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CD2 is expressed on murine B cells, probably as a result of a chromosomal translocation event during speciation. There are no activating antibodies to mouse CD2, but when activated non-specifically, only T cells up-regulate their expression of CD2. We investigated the expression and function of CD2 on B cells using mice transgenic for human CD2 under the control of a modified version of the autologous promoter/enhancer that included the immunoglobulin enhancer. This construction directs expression of human CD2 to the B cell compartment as well as to the T cell compartment. In this paper, we confirm that activating pairs of anti-CD2 monoclonal antibodies are mitogenic for mouse T cells transgenic for human CD2. In contrast, mouse B cells that express similar amounts of human CD2 are not stimulated to proliferate by equivalent doses of these antibodies. We were also unable to show any functional consequence for these B cells as a result of CD2 ligation. [ABSTRACT FROM AUTHOR]

Human multinegative (CD3- 4- 8- 1 9- ; MN) thymocytes proliferate optimally in response to anti-CD2 plus anti-CD28 mAb plus PMA or IL-7. The role of CD45 was assessed by the addition of mAb to a CD45 common determinant, or to CD45RA. MN thymocytes are unresponsive to anti-CD2 mAb. Co-stimulation with anti-CD45RA generated 1.6-5.7-fold enhancement of a proliferative response, with maximal enhancement by cross-linkage of CD45RA molecules. The response to anti- CD2/28 mAb was reproducibly enhanced only by immobilized anti-CD45RA. Cross-linking of CD45RA and CD28 through the use of heteroconjugates of mAb did not enhance the co-stimulation by CD45RA. The most marked enhancement by anti-CD45RA occurred in suboptimal activation conditions. In contrast, the response to anti-CD2 or anti-CD2/28 was inhibited by mAb to CD45 common determinants (anti-CD45) in the presence or absence of PMA or IL-7, with the most profound inhibition (6-8-fold) detected in optimal proliferative conditions. Cross-linking of CD45 and CD28 through heteroconjugates of mAb was required as soluble anti-CD45 or immobilized anti-CD45 were unable to mediate inhibition. This inhibitory effect of (anti-CD45 × 28) was specific to MN thymocytes as no inhibition was detectable when peripheral blood T cells were treated with anti-CD2/28 and the same heteroconjugate. The differential effects of anti-CD45 and anti-CD45RA may reflect either CD45 heterogeneity on MN thymocytes, or the physical modulation of a single CD45 molecules by interactions at different epitopes, and the avidity of the relevant CD45 mAb for thymocyte CD45 isoforms may play a role. We conclude that the molecular associations between signal transduction molecules on progenitor thymocytes differ significantly from those assembled on peripheral blood T cells. [ABSTRACT FROM AUTHOR]

The baculovirus expression system was used to produce three different constructs of the murine cell surface adhesion receptor CD2. One construct coded for a single, N-terminal, Ig-fold domain. It was inefficiently secreted and therefore primarily intracellular. The second construct coded for both extracellular, N-terminal Ig-fold domains. This was efficiently secreted into culture supernatant. The third construct coded for the full-length transmembrane molecule which localized to the cell surface. All constructs were monomers of predicted MW and were appropriately glycosylated. They retained epitopic specificity as demonstrated by binding to mAbs, and adhesion function as demonstrated by a rosetting assay. [ABSTRACT FROM AUTHOR]

Recent studies from several laboratories suggest that the rate of postnatal maturation of T-cell function(s) associated with in vitro activation may be slower in children at high genetic risk for atopy (HR), compared to their normal (low risk; LR) counterparts. The present study compared the in vitro activity of the function-associated surface molecules CD2, CD3 and CD28 in panels of 27 HR and 13 LR infants, with a reference panel of 10 adults. employing assay systems involving T-cell stimulation with MoAbs against these molecules. The response maxima induced by saturating levels of the MoAbs were equivalent in all 3 groups, but Tcells from the HR infants required 10-50 fold higher levels of anti-CD3 stimulation to attain their maximum response, relative to adults (p = 0.02); T-cells from LR infants were also less responsive to anti-CD3 than adults, but these differences were smaller and did not attain statistical significance. It is suggested that these differences are attributable to varying proportions of competent T-memory cells (which respond to low levels of anti-CD3) in PBL from these populations, the postnatal accumulation of which proceeds slowest in the HR group. [ABSTRACT FROM AUTHOR]

Unlabelled: Peripheral blood lymphocytes subsets were examined in 233 healthy school children aged 4.9-13.7 years at the time of examination. Lymphocyte subsets were characterized according to the following cluster of differentiation (CD) numbers: CD2, CD4, CD8 and CD19 and quantified according to both their absolute number and as a percentage of total lymphocytes. For the purpose of analysis, the LMS (lambda, mu, sigma) method was utilized, with a 3%-97% confidence interval. Smoothing of the generated curves, was by multiple regression analysis, using the least squares method. The results of these analyses indicate distinct trends as a child ages, both in absolute numbers and in the percentage of each cell type.Conclusion: We characterized lymphocyte subsets in children aged 4.8-13.7 years. These data should prove of considerable value to pediatricians dealing with patients with known or suspected immunological problems, and ought to be used in place of the commonly used, but inappropriate, adult lymphocyte subset ranges. [ABSTRACT FROM AUTHOR]

Eosinophils have a pivotal role in the pathogenesis of allergic airway disorders. They express a variety of receptors involved in their activation. Recently, the role of the CD2 Ig superfamily of receptors in eosinophilic inflammation, especially 2B4 and CD48, has been explored in allergic rhinitis and asthma. In recent years, there has been increasing evidence suggesting that these two molecules have an important role in allergic airway disorders. In this article, the most recently acquired data on the role of CD48 and 2B4 in allergic airway disorders are reviewed. [ABSTRACT FROM AUTHOR]

Simple Summary: T-cell lymphoblastic lymphoma (T-LBL) is extremely rare and aggressive with no practical risk model defined. Considering the controversies over the prognostic value of T-LBL immunological subtypes, we re-evaluated 49 subsequent adult T-LBL patients treated according to the German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia protocols, with 85.7% with complete remissions. To the best of our knowledge, this is the largest study of T-LBL diagnosed by flow-cytometry of the material obtained by fine-needle aspiration biopsy. We show that (1) CD2 status and age are powerful independent prognostic factors influencing overall survival and the risk of treatment failure; (2) the early/pro-T/CD2(−) subtype is associated with extremely poor outcomes; and (3) poor outcomes in ETP vs. non-ETP are strikingly consistent with the pro-T CD2(−) subtype. The lack of CD2 expression in T-LBL emerges as a new marker of an ultra-high-risk of treatment failure. We show here that ETP is a non-uniform entity, where the outcome depends on the CD2 status. (1) Background: T-cell lymphoblastic lymphoma (T-LBL) is extremely rare and highly aggressive, with no practical risk model defined yet. The prognostic value of T-LBL immunological subtypes is still a matter of controversy. (2) Methods: We re-evaluated 49 subsequent adult T-LBL patients treated according to the German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia (GMALL) protocols, 05/93 (n = 20) and T-LBL 1/2004 (n = 29), 85.7% of which achieved complete remission (CR). (3) Results: The 5/10-year overall survival (OS) and event-free survival (EFS) were 62%/59% and 48%/43%, respectively. In 96% of patients, flow cytometry analyses defining the WHO 2008 immunophenotypes were available. Cortical, early/pro-T/CD2(−), early/pre-T/CD2(+), and mature subtypes were identified in 59.5%, 19%, 15%, and 6.5% of patients, respectively. Overall, 20% of patients had the early T-cell precursor (ETP)-LBL immunophenotype, as proposed by the WHO 2017 classification. For the early/pro-T/CD2(−) subtype, the five-year OS and EFS were 13% and 13%, while for all the other, non-pro-T subtypes, they were 69% and 67%. By multivariate analysis, only CD2(−) status and age > 35 years emerged as strong, independent factors influencing OS and EFS, while the risk of CR failure was influenced by age only (>35 years). (4) Conclusions: ETP was non-significant for OS, unless an ultra-high-risk pro-T/CD2(−) subtype was concerned. [ABSTRACT FROM AUTHOR]

• Hydrogelation plays a significant role in the self-assembly and complexation with guest in sol. • Fluorescence switching ability of ChN, impart a suitable probe for the monitoring Cd2+ ions. • The reasonable description of the chelation mechanism and the kinetics for ChN/Cd2+ • Reverse fluorescence measurements with EDTA for the support of signal-on of free ChN. The hydrogel network regulates a significant role in the self-assembly, complexation and chelation with guest molecules like ions or small chemical moieties. In the present research work, a sensitive and greenish-yellow fluorescent hydrogel Chitosan/2-hydroxy-1-naphthaldehyde (ChN) has been prepared purposefully. Interestingly, springy and fluorescent ChN hydrogel shows excellent dual functionality, immobilization and quenching selectivity for Cd2+ ions by chelation in the sol phase. The "signal-off" behavior of ChN/Cd2+ has been established by the prominent chelation enhanced quenching mechanism (CHEQ) with a strong spin-orbit coupling. The fluorescence lifetime measurement and evaluation of Stern–Volmer relationship confirm the stability and selectivity of Cd2+ ions for ChN over other cations at a detection limit of 0.223 nM (S/N = 2). The reversibility of complexation or signal-on behavior of free ChN present in ChN/Cd2+ complex has been examined with a replaceable and strong chelating agent ethylene diamine tetra acetic acid. ChN is found to be credibly suitable for monitoring Cd2+ ions in aquatic environmental system. [ABSTRACT FROM AUTHOR]

NK cell ADCC supports monoclonal antibody anti-tumor therapies. We investigated serial ADCC and whether it could be predicted by NK phenotypes, including expression of CD16A, CD2 and perforin. CD16A, the NK receptor for antibodies, has AA158 valine or phenylalanine variants with different affinities for IgG. CD2, a costimulatory protein, associates with CD16A and can augment CD16A-signaling. Pore-forming perforin is essential for rapid NK-mediated killing. NK cells were monitored for their ADCC serial killing frequency (KF). KF is the average number of target cells killed per cell by a cytotoxic cell population. KF comparisons were made at 1:4 CD16pos NK effector:target ratios. ADCC was toward Daudi cells labeled with 51Cr and obinutuzumab anti-CD20 antibody. CD16A genotypes were determined by DNA sequencing. CD2, CD16A, and perforin expression was monitored by flow cytometry. Serial killing KFs varied two-fold among 24 donors and were independent of CD16A genotypes and perforin levels. However, high percentages of CD2pos of the CD16Apos NK cells and high levels of CD16A were associated with high KFs. ROC analysis indicated that the %CD2pos of CD16Apos NK cells can predict KFs. In conclusion, the extent of serial ADCC varies significantly among donors and appears predictable by the CD2posCD16Apos NK phenotype. [ABSTRACT FROM AUTHOR]

African swine fever virus (ASFV) is currently the most dreaded infectious disease affecting the global swine production industry. There is no commercial vaccine available, making the culling of infected animals the current solution to control outbreaks. Effective experimental vaccines have been developed by deleting virus genes associated with virulence. Deletion of the ASFV 9GL gene (∆9GL) has resulted in the attenuation of different ASFV strains, although the degree of attenuation varies across isolates. Here, we investigated the possibility of the increased safety of the experimental vaccine strain ASFV-G-Δ9GL by deleting two additional virus genes involved in pathogenesis, CD2v, a CD2 like viral encoded gene from the EP402R open reading frame (ORF), and C-type lectin-like viral gene, encoded from the EP153R ORF. Two new recombinant viruses were developed, ASFV-G-Δ9GL/ΔCD2v and ASFV-G-Δ9GL/ΔCD2v/ΔEP153R, harboring two and three gene deletions, respectively. ASFV-G-Δ9GL/ΔCD2v/ΔEP153R, but not ASFV-G-Δ9GL/ΔCD2v, had a decreased ability to replicate in vitro in swine macrophage cultures when compared with parental ASFV-G-Δ9GL. Importantly, ASFV-G-Δ9GL/ΔCD2v and ASFV-G-Δ9GL/ΔCD2v/ΔEP153R induced almost undetectable viremia levels when inoculated into domestic pigs and failed to protect them against challenge with parental virulent ASFV-Georgia, while ASFV-G-Δ9GL offered robust protection during challenge. Therefore, the deletion of CD2-like and C-type lectin-like genes significantly decreased the protective potential of ASFV-G-Δ9GL as a vaccine candidate. This study constitutes an example of the unpredictability of genetic manipulation involving the simultaneous deletion of multiple genes from the ASFV genome. [ABSTRACT FROM AUTHOR]

The genesis of gene families by the capture of host genes and their subsequent duplication is a crucial process in the evolution of large DNA viruses. CD48 is a cell surface molecule that interacts via its N-terminal immunoglobulin (Ig) domain with the cell surface receptor 2B4 (CD244), regulating leukocyte cytotoxicity. We previously reported the presence of five CD48 homologs (vCD48s) in two related cytomegaloviruses, and demonstrated that one of them, A43, binds 2B4 and acts as a soluble CD48 decoy receptor impairing NK cell function. Here, we have characterized the rest of these vCD48s. We show that they are highly glycosylated proteins that display remarkably distinct features: divergent biochemical properties, cellular locations, and temporal expression kinetics. In contrast to A43, none of them interacts with 2B4. Consistent with this, molecular modeling of the N-terminal Ig domains of these vCD48s evidences notable changes as compared to CD48, suggesting that they interact with alternative targets. Accordingly, we demonstrate that one of them, S30, tightly binds CD2, a crucial T- and NK-cell adhesion and costimulatory molecule. Thus, our findings show how a key host immune receptor gene captured by a virus can be subsequently remodeled to evolve new immunoevasins with altered binding properties. [ABSTRACT FROM AUTHOR]

T cell surfaces are covered with microvilli, actin-rich and flexible protrusions. We use super-resolution microscopy to show that ≥90% of T cell receptor (TCR) complex molecules TCRαβ and TCRζ, as well as the co-receptor CD4 (cluster of differentiation 4) and the co-stimulatory molecule CD2, reside on microvilli of resting human T cells. Furthermore, TCR proximal signaling molecules involved in the initial stages of the immune response, including the protein tyrosine kinase Lck (lymphocyte-specific protein tyrosine kinase) and the key adaptor LAT (linker for activation of T cells), are also enriched on microvilli. Notably, phosphorylated proteins of the ERM (ezrin, radixin, and moesin) family colocalize with TCRαβ as well as with actin filaments, implying a role for one or more ERMs in linking the TCR complex to the actin cytoskeleton within microvilli. Our results establish microvilli as key signaling hubs, in which the TCR complex and its proximal signaling molecules and adaptors are preassembled prior to activation in an ERM-dependent manner, facilitating initial antigen sensing. • Single-molecule microscopy maps signaling molecules on the resting T cell membrane • TCRαβ, TCRζ, CD4, CD2, Lck, and LAT are all highly enriched on microvilli • TCR localization is mediated by ERM proteins • Microvilli are hubs for TCR signaling, facilitating fast initial immune response T-cell surfaces are covered with microvilli, actin-rich and flexible protrusions. Ghosh et al. show that T cell receptor complex molecules, as well as several proximal signaling molecules, are preassembled on microvilli in an ERM-dependent manner. These results establish microvilli as key signaling hubs that facilitate initial antigen sensing by T cells. [ABSTRACT FROM AUTHOR]

Abstract: Visceral leishmaniasis (VL) commonly known as Kala-azar in India is one of the several clinically important infections, where Th1 sub-population of CD4+ T-cells, despite a pre-requisite, fails to express macrophage migration inhibition factor (MIF) and interferon-γ which both activate the macrophage and coordinate the immune response to intra-cellular Leishmania sp. Expression of CD2 receptors before and after antileishmanial therapy on CD4+ T-cells of VL patients and their corresponding effect on MIF were examined. Before treatment the number of T-cells expressing CD2 was low which incorporated insignificant MIF response. The immunological reconstitution was, however, observed after treatment as manifested through upregulation of CD2+ T-cells with pronounced MIF generation response. The study, therefore, identifies a possible role of CD2 antigen in immunity to VL. [Copyright &y& Elsevier]

We report a patient with a variant form of CD2+ acute promyelocytic leukemia (APL) who had double translocations (15;17) in a single leukemic cell. The patient presented with severe neutropenia, thrombocytopenia, and disseminated intravascular coagulation. The bone marrow showed marked hyperplasia with large leukemic cells that had bizarre nuclear configuration and basophilic, hypogranular cytoplasm. Leukemic cells were positive for CD2, 13, 33, 34, and 56 and negative for HLA-DR. The karyotype of the abnormal clone was characterized as 92,XXYY, t(15;17)(q22;q21)x2. No other additional abnormal clone was found, and the patient's condition was diagnosed as tetraploid APL variant. Fluorescence in situ hybridization assay revealed 2 promyelocytic leukemia and retinoic acid receptor alpha (PML/RARA) fusion signals, and reverse transcription-polymerase chain reaction assay revealed short-form PML/RARA fusion transcript. Tetraploidy in APL is a very rare abnormality. Double translocations were an additional abnormality in this case, and this patient's karyotype might have had some influence on morphological characteristics, expression of CD2, and poor clinical outcome. [ABSTRACT FROM AUTHOR]

T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) is a rare acute leukemia that expresses cytoplasmic CD3 (cCD3) and frequently lacks surface CD3. Given that routine flow cytometric testing for cCD3 may not be feasible and cCD3 interpretation may be difficult, we investigate if surface CD2 and/or CD7 expression on blasts can be used by flow cytometry to screen for T-lineage acute leukemia. We retrospectively reviewed flow cytometric data from 233 acute leukemias (36 T-ALL/LBL, 8 mixed-phenotype acute leukemia T/myeloid, 80 acute myeloid leukemia, 97 B-ALL/LBL, 8 mixed-phenotype acute leukemia B/myeloid, and 4 acute undifferentiated leukemia cases). Uniform expression (≥75% of blasts) of CD2 and/or CD7 was seen in all 44 cCD3-positive cases but in only 11% (20/189) of cCD3-negative acute leukemias, thus demonstrating 100% sensitivity and 89% specificity in the identification of cCD3-positive (T-lineage) acute leukemia. To avoid selection bias, we prospectively studied 232 consecutive acute leukemias for which cCD3, CD2, and CD7 were automatically performed in all cases. Similar to the retrospective study, uniform expression of CD2 and/or CD7 on blasts showed 100% sensitivity and 88% specificity in the screening for cCD3-positive (T-lineage) acute leukemia. Therefore, acute leukemias with uniform expression of CD2 and/or CD7 warrant further testing for cCD3 to evaluate for T-lineage acute leukemia. Blasts that lack both uniform CD2 and CD7 expression do not require additional cCD3 testing. We propose that CD2 and CD7 could be utilized in a limited antibody flow cytometry panel as a sensitive, robust, and cost-effective way to screen for T-lineage acute leukemia., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The spermatogonial stem cell (SSC) population in testis is small, and the lack of SSC markers has severely handicapped research on these cells. During our attempt to identify genes involved in SSC aging, we found that CD2 is expressed in cultured SSCs. Flow cytometric analysis and spermatogonial transplantation experiments showed that CD2 is expressed in SSCs from mature adult mouse testes. Cultured SSCs transfected with short hairpin RNAs (shRNAs) against CD2 proliferated poorly and showed an increased frequency of apoptosis. Moreover, functional analysis of transfected cells revealed impairment of SSC activity. Fluorescence activated cell sorting and spermatogonial transplantation experiments showed that CD2 is expressed not only in mouse but also in rat SSCs. The results indicate that CD2 is a novel SSC surface marker conserved between mouse and rat SSCs.

The affinity of T-cell receptors (TCRs) for major histocompatibility complex molecules (MHCs) presenting cognate antigens likely determines whether T cells initiate immune responses, or not. There exist few measurements of two-dimensional (2D) TCR-MHC interactions, and the effect of auxiliary proteins on binding is unexplored. Here, Jurkat T-cells expressing the MHC molecule HLA-DQ8-glia-α1 and the ligand of an adhesion protein (rat CD2) were allowed to bind supported lipid bilayers (SLBs) presenting fluorescently labelled L3-12 TCR and rat CD2, allowing measurements of binding unconfounded by cell signaling effects or co-receptor binding. The 2D K d (mean±s.d.), was only marginally influenced by including CD2 up to ∼200 bound molecules/μm 2 but higher CD2 densities reduced the affinity up to 1.9-fold. Cell-SLB contact size increased steadily with ligand density without affecting binding for contacts at up to ∼20% of total cell area, but beyond this lamellipodia appeared, giving an apparent increase in bound receptors of up to 50%. Our findings show how parameters other than the specific protein-protein interaction can influence binding behavior at cell-cell contacts.2 but higher CD2 densities reduced the affinity up to 1.9-fold. Cell-SLB contact size increased steadily with ligand density without affecting binding for contacts at up to ∼20% of total cell area, but beyond this lamellipodia appeared, giving an apparent increase in bound receptors of up to 50%. Our findings show how parameters other than the specific protein-protein interaction can influence binding behavior at cell-cell contacts., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Invariant natural killer T (iNKT) cells are innate-like CD1d-restricted T cells that express the invariant T cell receptor (TCR) composed of Vα24 and Vβ11 in humans. iNKT cells specifically recognize glycolipid antigens such as α-galactosylceramide (αGalCer) presented by CD1d. iNKT cells show direct cytotoxicity toward CD1d-positive tumor cells, especially when CD1d presents glycolipid antigens. However, iNKT cell recognition of CD1d-negative tumor cells is unknown, and direct cytotoxicity of iNKT cells toward CD1d-negative tumor cells remains controversial. Here, we demonstrate that activated iNKT cells recognize leukemia cells in a CD1d-independent manner, however still in a TCR-mediated way. iNKT cells degranulated and released Th1 cytokines toward CD1d-negative leukemia cells (K562, HL-60, REH) as well as αGalCer-loaded CD1d-positive Jurkat cells. The CD1d-independent cytotoxicity was enhanced by natural killer cell-activating receptors such as NKG2D, 2B4, DNAM-1, LFA-1 and CD2, but iNKT cells did not depend on these receptors for the recognition of CD1d-negative leukemia cells. In contrast, TCR was essential for CD1d-independent recognition and cytotoxicity. iNKT cells degranulated toward patient-derived leukemia cells independently of CD1d expression. iNKT cells targeted myeloid malignancies more than acute lymphoblastic leukemia. These findings reveal a novel anti-tumor mechanism of iNKT cells in targeting CD1d-negative tumor cells and indicate the potential of iNKT cells for clinical application to treat leukemia independently of CD1d., (© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

The glycoprotein CD2 is a costimulatory receptor expressed mainly on T and NK cells that binds to LFA3, a cell surface protein expressed on e.g., antigen-presenting cells. CD2 has an important role in the formation and organization of the immunological synapse that is formed between T cells and antigen-presenting cells upon cell-cell conjugation and associated intracellular signaling. CD2 expression is upregulated on memory T cells as well as activated T cells and plays an important role in activation of memory T cells despite the coexistence of several other costimulatory pathways. Anti-CD2 monoclonal antibodies have been shown to induce immune modulatory effects in vitro and clinical studies have proven the safety and efficacy of CD2-targeting biologics. Investigators have highlighted that the lack of attention to the CD2/LFA3 costimulatory pathway is a missed opportunity . Overall, CD2 is an attractive target for monoclonal antibodies intended for treatment of pathologies characterized by undesired T cell activation and offers an avenue to more selectively target memory T cells while favoring immune regulation., (Copyright © 2020 Binder, Cvetkovski, Sellberg, Berg, Paternina Visbal, Sachs, Berglund and Berglund.)

The interaction between CD2-associated protein (CD2AP) and CD2 plays a vital role in lymphocyte adhesion and T cells activation in mammals. In this study, a CD2AP gene (GenBank accession number: MK579862; designated as On-CD2AP) was identified from tilapia (Oreochromis niloticus). Sequence analysis showed that On-CD2AP protein shares high similarity with mammals, including three Src homology 3 (SH3) domains, a section of poly proline motif and a coiled coil region. Transcription levels of On-CD2AP were detected in nine tissues of healthy Nile tilapia, and the highest expression levels were detected in the spleen and gill. On-CD2AP were significantly up-regulated in thymus, head kidney and brain after infected by Streptococcus agalactiae, as well as in head kidney leukocytes (HKLs) with LPS and LTA stimulation. Moreover, a section conserved pro-rich motif that are responsible for binding of CD2 to CD2AP were found in the CD2 cytoplasmic sequence of Nile tilapia (On-CD2C). A weak interaction between On-CD2AP and On-CD2C was proved by yeast two-hybrid assay. In addition, the recombinant proteins of CD2AP-His (rOn-CD2AP-His) and GST-CD2C (GST-rOn-CD2C) were obtained through prokaryotic expression system. His pull-down assay showed that rOn-CD2AP-His and GST-rOn-CD2C could bind to each other. These findings indicate that CD2AP is crucial in immune response during S.agalactiae infection, and the mechanism of interaction between CD2AP and CD2 is conservative in Nile tilapia., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Characteristic of allergic asthma, CD4+Th2 lymphocytes secrete Th2 cytokines, interleukin (IL)-4, IL-13, and IL-5 that mediate the inflammatory immune response. Surface expression of CD2 and its ligand, CD58, is increased on the monocytes and eosinophils of asthma patients, which correlate with elevated serum IgE levels, suggesting that CD2 may contribute to allergic airway inflammation. Using a murine model of asthma, we observed that house dust mice extract (HDME)-exposed Balb/c mice have increased airway hyperresponsiveness (AHR), lung inflammation, goblet cell hyperplasia, and elevated levels of Th2 cytokines in the lungs, as well as increased serum IgE levels as compared to the control mice. In contrast, with the exception of serum IgE levels, all the other parameters were significantly reduced in HDME-treated Cd2 -/- mice. Interestingly, Il13 but not Il4 or Il5 gene expression in the lungs was dramatically decreased in HDME-exposed Cd2 -/- mice. Given the established role of IL-13 in promoting goblet cell hyperplasia, lung inflammation and AHR in allergic asthma, our studies reveal a unique role for CD2 in the regulation of Th2-associated allergic asthma.Cd2 -/- mice. Consistently, gene expression of microRNAs regulating mucin production, inflammation, airway smooth muscle cell proliferation and IL-13 transcripts were increased in the lungs of HDME-exposed Cd2 -/- mice. Given the established role of IL-13 in promoting goblet cell hyperplasia, lung inflammation and AHR in allergic asthma, our studies reveal a unique role for CD2 in the regulation of Th2-associated allergic asthma., (Copyright © 2020 Hashem, Kammala, Thaxton, Griffin, Mullany, Panettieri, Subramanian and Das.)

The interplay between keratinocytes and immune cells, especially T cells, plays an important role in the pathogenesis of chronic inflammatory skin diseases. During psoriasis, keratinocytes attract T cells by releasing chemokines, while skin-infiltrating self-reactive T cells secrete proinflammatory cytokines, e.g., IFNγ and IL-17A, that cause epidermal hyperplasia. Similarly, in chronic graft-versus-host disease, allogenic IFNγ-producing Th1/Tc1 and IL-17-producing Th17/Tc17 cells are recruited by keratinocyte-derived chemokines and accumulate in the skin. However, whether keratinocytes act as nonprofessional antigen-presenting cells to directly activate naive human T cells in the epidermis remains unknown. Here, we demonstrate that under proinflammatory conditions, primary human keratinocytes indeed activate naive human T cells. This activation required cell contact and costimulatory signaling via CD58/CD2 and CD54/LFA-1. Naive T cells costimulated by keratinocytes selectively differentiated into Th1 and Th17 cells. In particular, keratinocyte-initiated Th1 differentiation was dependent on costimulation through CD58/CD2. The latter molecule initiated STAT1 signaling and IFNγ production in T cells. Costimulation of T cells by keratinocytes resulting in Th1 and Th17 differentiation represents a new explanation for the local enrichment of Th1 and Th17 cells in the skin of patients with a chronic inflammatory skin disease. Consequently, local interference with T cell-keratinocyte interactions may represent a novel strategy for the treatment of Th1 and Th17 cell-driven skin diseases.

Expansion of natural killer (NK) cells expressing NKG2C occurs following human cytomegalovirus (HCMV) infection and is amplified by human immunodeficiency virus (HIV) co-infection. These NKG2C-expressing NK cells demonstrate enhanced CD16-dependent cytokine production and downregulate FcεRIγ and promyelocytic leukemia zinc finger protein (PLZF). Lacking NKG2C diminishes resistance to HIV infection, but whether this affects NK cell acquisition of superior antibody-dependent function is unclear. Therefore, our objective was to investigate whether HCMV-driven NK cell differentiation is impaired in NKG2Cnull HIV-infected individuals. Phenotypic (CD2, CD16, CD57, NKG2A, FcεRIγ, and PLZF expression) and functional (cytokine induction and cytotoxicity) properties were compared between HIV–infected NKG2Cnull and NKG2C-expressing groups. Cytokine production was compared following stimulation through natural cytotoxicity receptors or through CD16. Cytotoxicity was measured by anti-CD16-redirected lysis and by classical antibody-dependent cell-mediated cytotoxicity (ADCC) against anti-class I human leukocyte antigen (HLA) antibody-coated cells. Our data indicate highly similar HCMV-driven NK cell differentiation in HIV infection with or without NKG2C. While the fraction of mature (CD57pos) NK cells expressing CD2 (p = 0.009) or co-expressing CD2 and CD16 (p = 0.03) was significantly higher in NKG2Cnull HIV-infected individuals, there were no significant differences in NKG2A, FcεRIγ, or PLZF expression. The general phenotypic and functional equivalency observed suggests NKG2C-independent routes of HCMV-driven NK cell differentiation, which may involve increased CD2 expression. [ABSTRACT FROM AUTHOR]

Background: Pediatric mastocytosis differs from adult mastocytosis in its presentation and clinical course. However, the data regarding the immunophenotypic characterization of mast cells in children are limited. Our objective was to evaluate the immunophenotype of mast cells in pediatric mastocytosis and correlate it with the clinical course., Methods: Biopsy specimens of children with cutaneous mastocytosis were retrieved from the institutions of pathology and were stained for CD25, CD2, and CD30. The percentage of mast cells and the staining intensity were correlated with the clinical data., Results: Twenty-five biopsy specimens were included in the study. Patients' average age was 15.4 at presentation and 37.5 months at biopsy performance. Clinical presentations included maculopapular cutaneous mastocytosis in 79% and mastocytoma in 21% of cases. CD25, CD2, and CD30 were positive in 60%, 44%, and 84% of the biopsy specimens, respectively. The staining score was significantly higher for CD30 as compared to those for CD25 and CD2 (P = 0.02). No correlation was found between the immunophenotype and the clinical form or course of disease., Conclusions: Our results confirm that CD30 is a sensitive marker for pediatric-onset mastocytosis. Nevertheless, its expression does not correlate with clinical subtype or clinical course. The sensitivity of CD25 is higher than that of CD2 in skin lesions., (© 2019 Wiley Periodicals, Inc.)

Objectives: Acute leukemia (AL) is a highly heterogeneous malignant disease caused by hematopoietic cell abnormalities. Our study investigated the potential for immunophenotyping of leukemic cells via flow cytometry and the clinical usefulness of this approach in treatment of AL., Methods: Bone marrow (BM) specimens were collected to detect antigen expression on hematopoietic cells in pre-treatment samples from patients with AL. In addition, fraction survival curves were calculated using the Kaplan-Meier method to explore the effect of markers on prognosis in AL., Results: Expression levels of immunophenotypic markers in patients with acute lymphoblastic leukemia (ALL) were significantly different from those in patients with acute myeloid leukemia (AML). In addition, there was a potential association between the surface marker, cluster of differentiation 2 (CD2), and fraction survival in AML. However, no similar result was found in ALL. Moreover, genetic tests showed greater positive variation of the break point cluster-Abelson tyrosine kinase ( BCR-ABL) fusion gene in samples from patients with ALL than in samples from patients with AML., Conclusions: We have shown a rapid and effective flow cytometry method that enables the identification of immunophenotype in AL. Moreover, CD2 may constitute a predictive marker for prognosis in patients with AML.