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This study assesses a plausible correlation between a dust intrusion episode and a daily increase in COVID-19 cases. A surge in COVID-19 cases was observed a few days after a Middle East Dust (MED) event that peaked on 25th April 2020 in southwest Iran. To investigate potential causal factors for the spike in number of cases, cross-correlations between daily combined aerosol optical depths (AODs) and confirmed cases were computed for Khuzestan, Iran. Additionally, atmospheric stability data time series were assessed by covering before, during, and after dust intrusion, producing four statistically clustered distinct city groups. Groups 1 and 2 had different peak lag times of 10 and 4-5 days, respectively. Since there were statistically significant associations between AOD levels and confirmed cases in both groups, dust incursion may have increased population susceptibility to COVID-19 disease. Group 3 was utilized as a control group with neither a significant level of dust incursion during the episodic period nor any significant associations. Group 4 cities, which experienced high dust incursion levels, showed no significant correlation with confirmed case count increases. Random Forest Analysis assessed the influence of wind speed and AOD, showing relative importance of 0.31 and 0.23 on the daily increase percent of confirmed cases, respectively. This study may serve as a reference for better understanding and predicting factors affecting COVID-19 transmission and diffusion routes, focusing on the role of MED intrusions. Supplementary Information The online version contains supplementary material available at 10.1007/s11356-021-18195-7.

Recently, nanomaterials have attracted attention in the field of pavement construction as modifiers to endure heavy loads and climate changes. In this study, conventional asphalt (bitumen) of penetration grade AC (60/70) was modified with graphene platelets (GnPs) at three different contents: 0.5%, 1.0%, and 1.5% by weight of asphalt content. Kinematic viscosity, softening point, penetration, and dynamic shear rheology tests were performed to evaluate the mechanical properties of modified binder. The results showed that adding GnPs improves the mechanical properties of asphalt binder, the kinematic viscosities, softening points, and rutting parameters increased but penetrations decreased with the contents of GnPs. Hot mix asphalt specimens with GnPs-modified asphalt were prepared and characterized with Marshall tests, thermal stress restrained specimen tests (TSRST), wheel tracking tests, and indirect tensile tests. Similar to the results of asphalt binder, the mechanical properties of asphalt mixture were improved by GnPs. Marshall stability increased by 21% and flow decreased by 24% with accepted value of 2.8 mm in penetration when the mixture was modified with 1.0 wt% of GnPs. At the same GnPs content, modified asphalt mixture led to lower failure temperature by 2 °C in comparison with unmodified asphalt mixture and the cryogenic failure stress was improved by 12%. The wheel tracking tests showed that GnPs-modified asphalt mixture has outstanding deformation resistance in comparison with unmodified asphalt mixtures: after 5000 cycles, 1.0 wt% of GnPs reduced the rut depth of asphalt mixture by 60%—the rut depth of unmodified asphalt mixture was 6.9 mm compared to 2.75 mm for modified asphalt mixture. After 10,000 cycles, the modified asphalt mixture showed rut depth of 3.24 mm in comparison with 8.12 mm in case of unmodified asphalt mixture. Addition of GnPs into asphalt mixture significantly improved the indirect tensile strength: 1.0 wt% of GnPs increased the indirect tensile strength of unmodified asphalt mixture from 0.79 to 1.1 MPa recording ~40% increment. The results of this study can confirm that graphene platelets enhance the mechanical properties of asphalt mixture and its performance.

Developing sustainable concrete with less ordinary Portland cement is a growing issue in the construction industry. Incorporating industrial by-products (such as fly ash or slag) or municipal solid wastes (such as waste glass or recycled concrete aggregate) into the concrete becomes an effective way to reduce the consumption of natural sources and carbon dioxide emission if a proper mix design is provided. The present study examines the influence of the combined use of off-ASTM Class F fly ash (FFA) and waste limestone powder (LSP) on flowability, compressive strength, and expansion characteristics of mortar mixtures containing waste glass sand (WGS). FFA and LSP were used as cement replacement while WGS was used as partial reactive siliceous river sand replacement. Material variables included different WGS replacement ratios (25%, 50%, and 75%) with river sand, LSP contents (25%, 50%, and 75%), FFA contents (15%, 30%, and 45%), and different combinations of FFA-LSP (15–10%, 15–15%, 15–30%, and 15–35%). It is shown that the single use of FFA or LSP reduces both compressive strength and flowability of mortar mixture as its replacement level increases. However, mixtures combined with FFA and LSP provide higher or comparable strength to the single LSP or FFA mixture. For the expansion characteristics due to alkali-silica reaction, the single-use of more than 30% FFA or 75% LSP has less than 0.1% expansion, which is a non-reactive aggregate criterion based on the C1260/C1567 when the test period is extended to 56 days. Moreover, the combination of FFA and LSP has a considerable reduction in expansion rate compared to the single FFA or LSP mixture.

Currently marketed influenza vaccines only confer protection against matching influenza virus strains. The influenza A composition of these vaccines needs to be annually updated. Vaccines that target conserved epitopes of influenza viruses would in principle offer broad cross-protection against influenza A viruses. In our study, we investigated the specific immune responses and protective efficacy of protein nanoparticles based on fusion proteins of flagellin carrier linked to conserved influenza epitopes. We first designed the fusion protein by replacing the hyperimmunogenic region of flagellin (FliC) with four tandem copies of the ectodomain of matrix protein 2 (f4M2e), H1 HA2 domain (fHApr8) or H3 HA2 domain (fHAaichi). Protein nanoparticles fabricated from these fusion proteins by using DTSSP crosslinking retained Toll-like receptor 5 agonist activity of FliC. Intranasal immunization with f4M2e, f4M2e/fHApr8 or f4M2e/fHAaichi nanoparticles induced vaccine antigen-specific humoral immune responses. It was also found that the incorporation of the H1 HA2 domain into f4M2e/fHApr8 nanoparticles boosted M2e specific antibody responses. Immunized mice were fully protected against lethal doses of virus challenge.

Nanoparticulate and molecular adjuvants have shown great efficacy in enhancing immune responses, and the immunogenic vaccines of the future will most likely contain both. To investigate the immunostimulatory effects of molecular adjuvants on nanoparticle vaccines, we have designed ovalbumin (OVA) protein nanoparticles coated with two different adjuvants—flagellin (FliC) and immunoglobulin M (IgM). These proteins, derived from Salmonella and mice, respectively, are representatives of pathogen‐ and host‐derived molecules that can enhance immune responses. FliC‐coated OVA nanoparticles, soluble FliC (sFliC) admixed with OVA nanoparticles, IgM‐coated nanoparticles, and OVA‐coated nanoparticles were assessed for immunogenicity in an in vivo mouse immunization study. IgM coatings on nanoparticles significantly enhanced both antibody and T cell responses, and promoted IgG2a class switching but not affinity maturation. FliC‐coated nanoparticles and FliC‐admixed with nanoparticles both triggered IgG2a class switching, but only FliC‐coated nanoparticles enhanced antibody affinity maturation. Our findings that affinity maturation and class switching can be directed independently of one another suggest that adjuvant coatings on nanoparticles can be tailored to generate specific vaccine effector responses against different classes of pathogens.

Glaucoma is associated with damage and death of optic nerve fibers within the Lamina Cribrosa (LC) region of the Optic Nerve Head. The pathogenesis of the disease is unclear, and the anterior LC surface morphology of different individuals can be one of the possible contributor of glaucoma development and progression. The current study evaluates the relationship between the LC surface curvature and distribution of shear stresses on the LC surface. The patient-specific reconstructed ocular model was developed and analyzed in a finite element analysis software. In addition, the effect of elastic modulus of both sclera and LC on the shear stress was examined. Results showed that there is a correlation between the shear stress distribution and the curvature of the anterior LC surface. This finding highlights the potential significance of the LC morphology on the distribution of LC shear stress and require further investigation.

Dendritic cells (DCs) are major antigen-presenting cells that can efficiently prime and cross-prime antigen-specific T cells. Delivering antigen to DCs via surface receptors is thus an appealing strategy to evoke cellular immunity. Nonetheless, which DC surface receptor to target to yield the optimal CD8+ and CD4+ T cell responses remains elusive. Herein, we report the superiority of CD40 over 9 different lectins and scavenger receptors at evoking antigen-specific CD8+ T cell responses. However, lectins (e.g., LOX-1 and Dectin-1) were more efficient than CD40 at eliciting CD4+ T cell responses. Common and distinct patterns of subcellular and intracellular localization of receptor-bound αCD40, αLOX-1 and αDectin-1 further support their functional specialization at enhancing antigen presentation to either CD8+ or CD4+ T cells. Lastly, we demonstrate that antigen targeting to CD40 can evoke potent antigen-specific CD8+ T cell responses in human CD40 transgenic mice. This study provides fundamental information for the rational design of vaccines against cancers and viral infections., Highlights • Antigen delivery to DCs via CD40 is more efficient than through nine other receptors at eliciting CD8 T+ cell response. • Antigen delivery via lectins (e.g., LOX-1 and Dectin-1) is more efficient than CD40 at eliciting CD4+ T cell responses. The success of an immunotherapeutic vaccine for cancer is largely dependent on its ability to evoke potent cellular immunity. Although targeting antigens to dendritic cells (DCs) has been known to be an efficient strategy to evoke cellular immunity, which targeted receptors yield the optimal cellular immunity remained elusive. We report that targeting CD40, compared to 9 other DC receptors, results in the greatest levels of CD8+ cytotoxic T cell responses, while targeting lectins results in enhanced CD4+ helper T cell responses. The findings of this study will assist us in the rational design of immunotherapeutic vaccines against cancers.

The reduction of bromate to bromide was successfully achieved by bimetallic catalysts with NZVI support in continuous-flow reactors. The stability of NZVI-supported bimetallic catalysts was enhanced by decelerating the iron corrosion and sequential rapid passivation of the iron-Cu-Pd ensembles under optimized reaction conditions. Thus99% bromate removal can be continuously achieved for 11 h. The lifetime of the bimetallic catalyst was further enhanced and tested under different hydraulic retention time, catalyst loading, and initial bromate concentrations. At the optimized operation conditions, the catalyst showed a complete bromate reduction by 24 h and then the reactivity slowly decreased to 20% over the next 100 h. X-ray diffraction and X-ray photoelectron spectroscopy showed that the reactive NZVI support was oxidized to Fe(II) and Fe(III) along with Cu(0) oxidation to CuO, while the oxidation state of Pd did not change. Therefore, bromate reduction occurred on the surface of reactive NZVI support and Cu(0) particle, while Pd played a role as a hydrogenation catalyst that prolonged the lifetime of the bimetallic catalyst.

CS1 (CRACC/CD319/SLAMF7) is a member of SLAM (Signaling Lymphocyte Activation Molecule) family receptors and is expressed on NK cells, a subset of CD8(+) T lymphocytes, activated monocytes, mature dendritic cells and activated B cells. In NK cells, CS1 signaling induces cytolytic function of NK cells against targets whereas in B cells CS1 induces proliferation and autocrine cytokine production. CS1 is upregulated in multiple myeloma cells and contributes to clonogenic growth and tumorigenicity. However, the mechanism of CS1 upregulation is unknown. In this study, we analyzed the transcriptional regulation of human CS1 gene in NK and B cells. The promoter region of CS1 contains a Blimp-1/PRDM1 binding site and relative luciferase activities of successive deletion mutants of CS1 promoter were different between Blimp-1/PRDM1-positive and Blimp-1/PRDM1-negative cells. Proximal region of CS1 promoter contains a CAAT box and atypical TATA-box that might result in common transcription initiation at -29 nucleotides upstream of the ATG translation start codon. Electrophoretic Mobility Shift Assay (EMSA) and Chromatin Immunoprecipitation (ChIP) assays revealed Blimp-1/PRDM1 binds to the CS1 promoter region. Mutating the Blimp-1/PRDM1 site at -750 to -746 decreased the transcriptional activity of CS1 promoter implicating a trans-activating function of Blimp-1/PRDM1 in human CS1 gene regulation. The finding that Blimp-1/PRDM1 enhances transcription of CS1 gene in multiple myeloma cells may help in developing novel strategies for therapeutic intervention in multiple myeloma.

Influenza virus infection of neonates poses a major health concern, often resulting in severe disease and hospitalization. At present, vaccines for this at-risk population are lacking. Thus, development of an effective vaccine is an urgent need. In this study, we have used an innovative nonhuman primate neonate challenge model to test the efficacy of a novel TLR 7/8 agonist R848-conjugated influenza virus vaccine. The use of the intact virus represents a step forward in conjugate vaccine design because it provides multiple antigenic targets allowing for elicitation of a broad immune response. Our results show that this vaccine induces high-level virus-specific Ab- and cell-mediated responses in neonates that result in increased virus clearance and reduced lung pathology postchallenge compared with the nonadjuvanted virus vaccine. Surprisingly, the addition of a second TLR agonist (flagellin) did not enhance vaccine protection, suggesting that combinations of TLR that provide increased efficacy must be determined empirically. These data support further exploration of this new conjugate influenza vaccine approach as a platform for use in the at-risk neonate population.

Recurring influenza viruses pose an annual threat to public health. A time-saving, cost-effective and egg-independent influenza vaccine approach is important particularly when responding to an emerging pandemic. We fabricated coated, two-layer protein nanoclusters from recombinant trimeric hemagglutinin from an avian-origin H7N9 influenza A virus as an approach for vaccine development in response to an emerging pandemic. Assessment of the virus-specific immune responses and protective efficacy in mice immunized with the nanoclusters demonstrated that the vaccine candidates were highly immunogenic, able to induce protective immunity and long-lasting humoral antibody responses to this virus without the use of adjuvants. Because the advantages of the highly immunogenic coated nanoclusters also include rapid productions in an egg-independent system, this approach has great potential for influenza vaccine production not only in response to an emerging pandemic, but also as a replacement for conventional seasonal influenza vaccines.

2B4 (CD244), a member of the signaling lymphocyte-activation molecule (SLAM/CD150), is expressed on all NK cells, a subpopulation of T cells, monocytes and basophils. Human NK cells express two isoforms of 2B4, h2B4-A and h2B4-B that differ in a small portion of the extracellular domain. In the present investigation, we have studied the functions of h2B4-A and h2B4-B. Our study demonstrated that these two isoforms differ in their binding affinity for CD48, which results in differential cytotoxic activity as well as intracellular calcium release by NK cells upon target cell recognition. Analysis of the predicted 3-D structure of the two isoforms showed conformational differences that could account for their differences in binding affinity to CD48. h2B4-A was able to mediate natural cytotoxicity against CD48-expressing K562 target cells and induce intracellular calcium release, whereas h2B4-B showed no effects. NK-92MI, U937, THP-1, KU812, primary monocytes, basophils and NK cells showed expression of both h2B4-A and h2B4-B whereas YT and IL-2-activated NK cells did not show any h2B4-B expression. Stimulation of NK cells through 2B4 resulted in decreased mRNA levels of both h2B4-A and h2B4-B indicating that down-regulation of 2B4 isoforms may be an important factor in controlling NK cell activation during immune responses.

2B4 (CD244), a member of the CD2 subset of the immunoglobulin superfamily, is important for stimulating human natural killer (NK) cell cytotoxicity and cytokine production. It is expressed on all NK cells, a subpopulation of T cells, monocytes, basophils and eosinophils. 2B4 interaction with its ligand CD48 regulates NK, T and B lymphocyte functions and thus plays a central role in various immune responses. Previous study indicated a role for AP-1 and Ets in the transcription of the 2B4 gene. In this study we report that stimulation of NK cells through surface 2B4 down-regulates its own expression due to a reduction in the promoter activity at the Ets element. The down-regulation of 2B4 could be a mechanism to attenuate the co-stimulatory signal from 2B4--CD48 interactions.

Gene expression profiling was used to compare the gene expression patterns of human germinal center (GC) T helper (Th) cells with other CD4+ T-cell subsets (naive, central, and effector memory T cells). GC-Th cells, specifically localized in germinal centers to help B cells, are distantly related to central and effector memory T cells in global gene expression profiles. GC-Th cells displayed substantial differences in mRNA for adhesion molecules, chemoattractant receptors, and cytokines compared with other populations. Distinct expression of transcriptional factors by GC-Th cells is consistent with the hypothesis that they may be different from other T cells in cell lineage. Interestingly, CXCL13, a critical chemokine for B-cell entry to lymphoid follicles, is one of the most highly up-regulated genes in GC-Th cells. GC-Th cells (but not other T cells) produce and secrete large amounts of functional CXCL13 upon T-cell receptor activation, a process that is dependent on costimulation, requires translation and transcription, and is dramatically enhanced by activation in the presence of GC-B cells. This study revealed for the first time the unique gene expression program of GC-Th cells.

Influenza virus can cause life-threatening infections in neonates and young infants. Although vaccination is a major countermeasure against influenza, current vaccines are not approved for use in infants less than 6 months of age, in part due to the weak immune response following vaccination. Thus, there is a strong need to develop new vaccines with improved efficacy for this vulnerable population. To address this issue, we established a neonatal African green monkey (AGM) nonhuman primate model that could be used to identify effective influenza vaccine approaches for use in young infants. We assessed the ability of flagellin, a Toll-like receptor 5 (TLR5) agonist, to serve as an effective adjuvant in this at-risk population. Four- to 6-day-old AGMs were primed and boosted with inactivated PR8 influenza virus (IPR8) adjuvanted with either wild-type flagellin or inactive flagellin with a mutation at position 229 (m229), the latter of which is incapable of signaling through TLR5. Increased IgG responses were observed following a boost, as well as at early times after challenge, in infants vaccinated with flagellin-adjuvanted IPR8. Inclusion of flagellin during vaccination also resulted in a significantly increased number of influenza virus-specific T cells following challenge compared to the number in infants vaccinated with the m229 adjuvant. Finally, following challenge infants vaccinated with IPR8 plus flagellin exhibited a reduced pathology in the lungs compared to that in infants that received IPR8 plus m229. This study provides the first evidence of flagellin-mediated enhancement of vaccine responses in nonhuman primate neonates. IMPORTANCE Young infants are particularly susceptible to severe disease as a result of influenza virus infection. Compounding this is the lack of effective vaccines for use in this vulnerable population. Here we describe a vaccine approach that results in improved immune responses and protection in young infants. Incorporation of flagellin during vaccination resulted in increased antibody and T cell responses together with reduced disease following virus infection. These results suggest that flagellin may serve as an effective adjuvant for vaccines targeted to this vulnerable population.

CS1 (CRACC, CD319, SLAMF7) is a member of the Signaling Lymphocyte Activation Molecule family expressed on immune cells mediating host defense. CS1 is a self-ligand and has both activating and inhibitory functions in Natural Killer cells. However, the function of CS1 in human monocytes is currently unknown. The objective of this study was to evaluate the control of CS1 surface expression in activated monocytes and to assess the effect of CS1 triggering on proinflammatory cytokine production by monocytes.Human monocytes were isolated from PBMC of healthy volunteers by magnetic depletion method or FACS sorting. The monocytes were cultured with or without LPS (1 μg/ml) in the presence or absence of various pharmacological inhibitors to inhibit NF-кB and PI3K signaling pathways. The cells were stimulated with anti-CS1 antibody or isotype control. Total RNA was extracted and RT-PCR was performed using specific primers for CS1 and EAT-2. Cell supernatants were collected and cytokine levels (TNF-α and IL-12p70) were determined by sandwich ELISA.Our study revealed that adherent or LPS-activated monocytes express CS1, and CS1 induction is via NF-кB and PI3K pathways. Importantly, cross-linking CS1 resulted in reduced production of proinflammatory cytokines TNF-α and IL-12p70 by LPS-activated monocytes.Our study demonstrated that CS1 plays an inhibitory role in human monocytes to control proinflammatory immune responses.

SummaryCS1 (CRACC, CD319) and 2B4 (CD244), members of the signalling lymphocyte activation molecule (SLAM) family receptors, regulate various immune functions. Genes encoding SLAM family receptors are located at 1q23, implicated in systemic lupus erythematosus (SLE). In this study, we have investigated the expression and alternative splicing of CS1 and 2B4 in immune cells from SLE patients. The surface expression of CS1 and 2B4 on total peripheral blood mononuclear cells (PBMCs), T, B, natural killer (NK) cells and monocytes in 45 patients with SLE and 30 healthy individuals was analysed by flow cytometry. CS1-positive B cell population was increased significantly in SLE patients. Because CS1 is a self-ligand and homophilic interaction of CS1 induces B cell proliferation and autocrine cytokine secretion, this could account for autoreactive B cell proliferation in SLE. The proportion of NK cells and monocytes expressing 2B4 on their surface was significantly lower in patients with SLE compared to healthy controls. Our study demonstrated altered expression of splice variants of CS1 and 2B4 that mediate differential signalling in PBMC from patients with SLE.

The complex morphologies of mineralised collagen fibrils are regulated through interactions between the collagen matrix and non-collagenous extracellular proteins. In the present study, poly-vinylphosphonic acid, a biomimetic analogue of matrix phosphoproteins, was synthesised and confirmed with FTIR and NMR. Biomimetic mineralisation of reconstituted collagen fibrils devoid of natural non-collagenous proteins was demonstrated with TEM using a Portland cement-containing resin composite and a phosphate-containing fluid in the presence of polyacrylic acid as sequestration, and poly-vinylphosphonic acid as templating matrix protein analogues. In the presence of these dual biomimetic analogues in the mineralisation medium, intrafibrillar and extrafibrillar mineralisation via bottom-up nanoparticle assembly based on the non-classical crystallisation pathway could be identified. Conversely, only large mineral spheres with no preferred association with collagen fibrils were observed in the absence of biomimetic analogues in the medium. Mineral phases were evident within the collagen fibrils as early as 4 h after the initially-formed amorphous calcium phosphate nanoprecursors were transformed into apatite nanocrystals. Selected area electron diffraction patterns of highly mineralised collagen fibrils were nearly identical to those of natural bone, with apatite crystallites preferentially aligned along the collagen fibril axes. Published by Elsevier Ltd.

2B4 (CD244), a member of the signaling lymphocyte-activation molecule (SLAM/CD150), is expressed on all NK cells, a subpopulation of T cells, monocytes and basophils. Human NK cells express two isoforms of 2B4, h2B4-A and h2B4-B that differ in a small portion of the extracellular domain. In the present investigation, we have studied the functions of h2B4-A and h2B4-B. Our study demonstrated that these two isoforms differ in their binding affinity for CD48, which results in differential cytotoxic activity as well as intracellular calcium release by NK cells upon target cell recognition. Analysis of the predicted 3-D structure of the two isoforms showed conformational differences that could account for their differences in binding affinity to CD48. h2B4-A was able to mediate natural cytotoxicity against CD48-expressing K562 target cells and induce intracellular calcium release, whereas h2B4-B showed no effects. NK-92MI, U937, THP-1, KU812, primary monocytes, basophils and NK cells showed expression of both h2B4-A and h2B4-B whereas YT and IL-2-activated NK cells did not show any h2B4-B expression. Stimulation of NK cells through 2B4 resulted in decreased mRNA levels of both h2B4-A and h2B4-B indicating that down-regulation of 2B4 isoforms may be an important factor in controlling NK cell activation during immune responses.

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease, characterized by the improper regulation of B lymphocytes that leads to the production of auto-antibodies. Several studies have identified a genetic susceptibility region called Sle 1 in mice and some human subjects. Recently, genomic characterization of the Sle1b locus, identified a highly polymorphic cluster of genes coding for the signaling lymphocyte activation molecule (SLAM)-related receptors (SRRs). 2B4 (CD244), CS1 (CD319, CRACC) and NTB-A are members of SRRs and are expressed on NK, T, B cells and monocytes. The aim of this study was to investigate expression of members of the SRRs in peripheral blood mononuclear cells (PBMC) from patients with SLE. We analyzed PBMC from forty-six patients with SLE and thirty-one healthy individuals. The surface expressions of 2B4, CS1, and NTB-A on T cells, B cells, NK cells, and monocytes were analyzed by flow cytometry. 2B4 expression was upregulated on T cells but down-regulated on NK cells and monocytes in patients with SLE. B cells from patients with SLE significantly overexpressed CS1 compared to B cells from healthy controls. The surface expression of NTB-A was upregulated on T cells and monocytes, but down-regulated on B cells in patients with SLE. Our results suggest that altered expression of SRRs may be related to the abnormal B cell hyperactivity in patients with SLE. (Research supported by grants from Texas Higher Education Board and UNTHSC).

Background The function of CD57+ CD4+ T cells, constituting a major subset of germinal center T (GC-Th) cells in human lymphoid tissues, has been unclear. There have been contradictory reports regarding the B cell helping function of CD57+ GC-Th cells in production of immunoglobulin (Ig). Furthermore, the cytokine and co-stimulation requirement for their helper activity remains largely unknown. To clarify and gain more insight into their function in helping B cells, we systematically investigated the capacity of human tonsil CD57+ GC-Th cells in inducing B cell Ig synthesis.