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The view of prostate cancer (PCa) progression as a result of the interaction of epithelial cancer cells with the host's immune system is supported by the presence of tumor infiltrating lymphocytes (TILs). TILs fate and interaction with the tumor microenvironment is mediated by accessory molecules such as CD5 and CD6, two signal-transducing coreceptors involved in fine-tuning of T cell responses. While the nature of the CD5 ligand is still controversial, CD6 binds CD166/ALCAM, a cell adhesion molecule involved in progression and dissemination of epithelial cancers, including PCa. The purpose of the present study was to determine the role of CD5, CD6, and CD166/ALCAM gene variants in PCa.Functionally relevant CD5 (rs2241002 and rs2229177), CD6 (rs17824933, rs11230563, and rs12360861) and CD166/ALCAM (rs6437585, rs579565, rs1044243, and rs35271455) single nucleotide polymorphisms (SNPs) were genotyped in germline DNA samples from 376 PCa patients. Their association with PCa prognostic factors, namely biochemical recurrence (BCR) and International Society of Urological Pathology (ISUP) grade was analyzed by generalized linear models and survival analyses.Proportional hazards regression showed that the minor CD6 rs12360861The results show the impact on PCa aggressiveness and recurrence brought about by gene variants involved in modulation of lymphocyte activation (CD5, CD6) and immune-epithelial cell adhesion (CD166/ALCAM) in PCa aggressiveness and recurrence, thus supporting a role for host immune response in PCa pathophysiology.

Multiple sclerosis (MS) is a chronic autoimmune disease with no curative treatment. The immune regulatory properties of type I IFNs have led to the approval of IFN-β for the treatment of relapsing-remitting MS. However, there is still an unmet need to improve the tolerability and efficacy of this therapy. In this work, we evaluated the sustained delivery of IFN-α1, either alone or fused to apolipoprotein A-1 by means of an adeno-associated viral (AAV) system in the mouse model of myelin oligodendrocyte glycoprotein–induced experimental autoimmune encephalomyelitis. These in vivo experiments demonstrated the prophylactic and therapeutic efficacy of the AAV–IFN-α or AAV–IFN-α fused to apolipoprotein A-1 vectors in experimental autoimmune encephalomyelitis, even at low doses devoid of hematological or neurologic toxicity. The sustained delivery of such low-dose IFN-α resulted in immunomodulatory effects, consisting of proinflammatory monocyte and T regulatory cell expansion. Moreover, encephalitogenic T lymphocytes from IFN-α–treated mice re-exposed to the myelin oligodendrocyte glycoprotein peptide in vitro showed a reduced proliferative response and cytokine (IL-17A and IFN-γ) production, in addition to upregulation of immunosuppressive molecules, such as IL-10, IDO, or PD-1. In conclusion, the results of the present work support the potential of sustained delivery of low-dose IFN-α for the treatment of MS and likely other T cell–dependent chronic autoimmune disorders.

Malgrat considerar-se una pràctica clínica de menor rellevància, la comunicació de males notícies en context sanitari és una de les tasques més difícil si amb major impacte emocional tant per a la persona atesa i els familiars propers com per al mateix metge. Si bé el pacient és, en aquest cas, l'eix central de la situació, tots els interlocutors experimenten dificultats pròpies que poden impedir una comunicació eficient, comportar conseqüències emocionals negatives i, en última instància, deteriorar la relació sanitària. En aquest sentit, és important reconèixer les veus de tots els protagonistes d'aquesta interacció i identificar quins són els reptes que cal afrontar a cada cas per poder atendre les seves necessitats i aconseguir una comunicació satisfactòria., A pesar de considerarse una práctica clínica de menor relevancia, la comunicación de malas noticias en contexto sanitario es una de las tareas más difíciles y con mayor impacto emocional tanto para la persona atendida y sus allegados como para el propio médico. Si bien el paciente es, en este caso, el eje central de la situación, los dos interlocutores experimentan dificultades propias que pueden impedir una comunicación eficiente, acarrear consecuencias emocionales negativas y, en última instancia, dañar la relación sanitaria. En este sentido, es importante reconocer las voces de todos los protagonistas de esta interacción e identificar cuáles son los desafíos que afrontan en cada caso para poder atender a sus necesidades y conseguir una comunicación satisfactoria., Despite being considered a less-relevant clinical practice, the communication of bad news is one of the tasks that is the most difficult and has the greatest emotional impact on the person being treated and their relatives, and the doctor themselves. Although the patient plays the most important role in this situation, the two interlocutors Comunicació de males notícies en context sanitari Marta Consuegra-Fernández, Alejandra Fernández-Trujillo (2021) Llengua, Societat i Comunicació, núm. 19 http://revistes.ub/index.php/LSC/ lsc@ub.edu http://creativecommons.org/licenses/by-nc-nd/4.0 doi:10.1344/LSC-2021.19.8 67each experience their own challenges, which can impede efficient communication. Eventually, this may have negative emotional consequences and ultimately damage the patient-provider relationship. In this sense, it is important to recognise the voices of all actors in this interaction and to identify the challenges they face. Achieving satisfactory communication means first recognising that the needs of each speaker have to be met.

Todo apunta a que el éxito contra la pandemia actual pasa por el desarrollo de una vacuna eficaz que proteja a la población del nuevo coronavirus. Esta protección llegaría a ser global y efectiva si una mayoría de personas recibe la vacuna. No obstante, el creciente movimiento antivacunas podría obstaculizar este efecto rebaño y prolongar la subsistencia del virus entre la población. El presente artículo pretende dar argumentos para un debate necesario sobre el rechazo de la vacunación, ineludible en contexto de emergencia sanitaria por la pandemia originada por SARS-CoV-2., The development of an effective vaccine that protects against the new coronavirus is expected to be the key to overcome the current pandemics. If the vaccine is administered to a majority of the people, this protection could eventually become global. Nevertheless, the growing anti-vaccine movement may hinder the herd effect and lengthen the virus persistence among the population. The present work argues in favor of a necessary debate on vaccination refusal, unavoidable within the framework of health emergency due to the SARS-CoV-2 pandemics., Universidad Pablo de Olavide

© Author(s) (or their employer(s)) 2020., [Background]: CD6 is a lymphocyte surface co-receptor physically associated with the T-cell receptor (TCR)/CD3 complex at the center of the immunological synapse. There, CD6 assists in cell-to-cell contact stabilization and modulation of activation/differentiation events through interaction with CD166/ALCAM (activated leukocyte cell adhesion molecule), its main reported ligand. While accumulating evidence is attracting new interest on targeting CD6 for therapeutic purposes in autoimmune disorders, little is known on its potential in cancer. In an attempt to elucidate the in vivo relevance of blocking CD6-mediated interactions in health and disease, we explored the consequences of expressing high circulating levels of a soluble form CD6 (sCD6) as a decoy receptor. [Methods]: High sCD6 serum levels were achieved by using transgenic C57BL/6 mice expressing human sCD6 under the control of lymphoid-specific transcriptional elements (shCD6LckEμTg) or wild type either transduced with hepatotropic adeno-associated virus coding for mouse sCD6 or undergoing repeated infusions of recombinant human sCD6 protein. Characterization of sCD6-induced changes was performed by ex vivo flow cytometry and functional analyses of mouse lymphoid organ cells. The in vivo relevance of those changes was explored by challenging mice with subcutaneous or metastatic tumors induced by syngeneic cancer cells of different lineage origins. [Results]: Through a combination of in vitro and in vivo studies, we show that circulating sCD6 expression induces defective regulatory T cell (Treg) generation and function, decreased CD166/ALCAM-mediated tumor cell proliferation/migration and impaired galectin-induced T-cell apoptosis, supporting the fact that sCD6 modulates antitumor lymphocyte effector function and tumorigenesis. Accordingly, sCD6 expression in vivo resulted in delayed subcutaneous tumor growth and/or reduced metastasis on challenge of mice with syngeneic cancer cells. [Conclusions]: Evidence is provided for the disruption of CD6 receptor-ligand interactions as a feasible immunomodulatory approach in cancer., This work was supported by the Worldwide Cancer Research (14-1275), Fundació La Marató TV3 (201319-30), and Ministerio de Economía y Competitividad (SAF-2016-80535-R) co-financed by European Development Regional Fund 'A way to achieve Europe' ERDF to FL; SAF2016-75195-R to JM, SAF2017-82905-R to RM, and SAF2015-70028-R to GG-A. ITS, MO-M, MV-dA, CC, SC-L and FA are recipients of fellowships from Fundação para a Ciência e a Tecnologia (SFRH/ BD/75738/2011), Ministerio de Economía y Competitividad (BES-2011-048415; BES-2014-069237; BES-2017-082107), Ministerio de Educación Cultura y Deporte (FPU15/02897), and Instituto de Salud Carlos III (Sara Borrell Programme, CD15/00016), respectively.

Psoriasis is a chronic inflammatory skin disease with a strong genetic background and is triggered by environmental factors. Available evidence supports CD6, a lymphocyte surface receptor mostly expressed by T cells, as a putative target in autoimmunity. Accordingly, a humanized anti-CD6 antibody has been assayed for the treatment of certain autoimmune disorders, including psoriasis. Here, we present novel evidence in mice and humans for a direct involvement of CD6 in psoriasis pathophysiology. First, an attenuated form of imiquimod-induced psoriasis-like skin inflammation was demonstrated in CD6-deficient mice, as deduced from lower epidermal thickness and local reduced production of pro-inflammatory cytokines, namely, interleukin-17A. Thus, isolated CD4(+)CD62L(+) T cells from CD6-deficient mice displayed decreased in vitro T-helper type 17 polarization. Second, a statistically significant association between CD6 single-nucleotide polymorphisms (rs17824933, rs11230563 and rs12360861) and more severe forms of psoriasis was demonstrated in a cohort of 304 patients at three public hospitals from the metropolitan area of Barcelona. Taken together, these results provide new supportive evidence of the contribution of the CD6 lymphocyte receptor in psoriasis at both experimental and clinical levels.

Primary Sjögren syndrome (SjS) is a systemic autoimmune disease that may affect 1 in 1000 people (overwhelmingly women) and that can be a serious disease with excess mortality due to severe organ-specific involvements and the development of B cell lymphoma; systemic involvement clearly marks the disease prognosis, and strongly suggests the need for closer follow-up and more robust therapeutic management. Therapy is established according to the organ involved and severity. As a rule, the management of systemic SjS should be organ-specific, with glucocorticoids and immunosuppressive agents limited to potentially-severe involvements; unfortunately, the limited evidence available for these drugs, together with the potential development of serious adverse events, makes solid therapeutic recommendations difficult. The emergence of biological therapies has increased the therapeutic armamentarium available to treat primary SjS. Biologics currently used in SjS patients are used off-label and are overwhelmingly agents targeting B cells, but the most recent studies are moving on into the evaluation of targeting specific cytokines involved in the SjS pathogenesis. The most recent etiopathogenic advances in SjS are shedding some light in the search for new highly-selective biological therapies without the adverse effects of the standard drugs currently used (corticosteroids and immunosuppressant drugs). This review summarizes the potential pharmacotherapeutic options targeting the main cytokine families involved in the etiopathogenesis of primary SjS and analyzes potential insights for developing new therapies. Fil: Retamozo, Maria Soledad. Laboratory of Autoimmune Diseases Josep Font; España. Hospital Privado Universitario de Córdoba; Argentina. Hospital Clínic de Barcelona; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina Fil: Flores Chavez, Alejandra. Laboratory of Autoimmune Diseases Josep Font; España. Mexican Institute for Social Security; México. Universidad de la Colima; México. Hospital Clínic de Barcelona; España Fil: Consuegra Fernández, Marta. Institut D'Investigacions Biomèdiques August Pi I Sunyer; España Fil: Lozano, Francisco. Institut D'Investigacions Biomèdiques August Pi I Sunyer; España. Hospital Clínic de Barcelona; España. Universidad de Barcelona; España Fil: Ramos Casals, Manuel. Laboratory of Autoimmune Diseases Josep Font; España. Universidad de Barcelona; España. Hospital Clínic de Barcelona; España Fil: Brito Zerón, Pilar. Laboratory of Autoimmune Diseases Josep Font; España. Hospital CIMA-Sanitas; España. Hospital Clínic de Barcelona; España

Sepsis is an unmet clinical need constituting one of most important causes of death world-wide, a fact aggravated by the appearance of multi-drug resistant (MDR) strains due to indiscriminate use of antibiotics. Host innate immune receptors involved in pathogen-associated molecular patterns (PAMPs) recognition represent a source of broad-spectrum therapies alternative or adjunctive to antibiotics. Among the few members of the ancient and highly conserved Scavenger Receptor Cysteine-Rich superfamily (SRCR-SF) sharing bacterial-binding properties there is CD6, a lymphocyte-specific surface receptor. Here, we analyze the bacterial-binding properties of three conserved short peptides (11-mer) mapping at extracellular SRCR domains of human CD6 (CD6.PD1, GTVEVRLEASW; CD6.PD2 GRVEMLEHGEW; CD6.PD3, GQVEVHFRGVW). All peptides show high binding affinity for PAMPs from Gram-negative (lipopolysaccharide; Kd from 3.5 to 3000 nM) and Gram-positive (lipotheichoic acid; Kd from 36 to 680 nM) bacteria. The CD6.PD3 peptide possesses broad bacterial-agglutination properties, and improved survival of mice undergoing polymicrobial sepsis in a dose- and time-dependent manner. Accordingly, CD6.PD3 triggers a decrease in serum levels of both pro-inflammatory cytokines and bacterial load. Interestingly, CD6.PD3 shows additive survival effects on septic mice when combined with Imipenem/Cilastatin. These results illustrate the therapeutic potential of peptides retaining the bacterial-binding properties of native CD6.

CD6 is a cell surface glycoprotein expressed by most T cells and a subset of B cells that has incompletely-defined roles in regulation of lymphocyte development, selection, activation and differentiation. The two main known mammalian CD6 ligands, CD166/ALCAM and the very recently reported CD318, are widely expressed by both immune cells and a wide range of other cell types, including various epithelial and mesenchymal cell types, as well as many neoplasms. Moreover, CD6 is also a receptor for several pathogen- and damage-associated molecular patterns. Further layers of complexity of CD6 function are implied by the existence of multiple CD6 isoforms generated by alternative splicing of CD6 transcripts and soluble forms of CD6 released by proteases from the lymphocyte surface. Multiple lines of evidence are now emerging to implicate CD6 and its ligands in the pathogenesis and potentially the treatment of human autoimmune diseases, such as multiple sclerosis and psoriasis. CD6 is an important multiple sclerosis risk gene, and mice genetically deficient in CD6 or CD318, or treated with antibodies or chimerical proteins that interfere with CD6-ligand interactions, are protected from experimental allergic encephalomyelitis, a mouse model of multiple sclerosis. CD6 deficient mice also show reduced TH17 differentiation and protection from disease in a moue model of psoriasis, providing a foundation for successful clinical trials of an anti-CD6 monoclonal antibody (Itolizumab) in psoriasis. Here we review current knowledge about CD6 and its ligands, and consider its potential value as a therapeutic target in a range of immune-mediated disorders.

CD5 was one of the first surface receptors described for mouse and human T lymphocytes. Since then, it has been found to be highly expressed by regulatory T cells and a subpopulation of regulatory B cells, to be physically associated with the T- and B-cell antigen receptors, to negatively modulate TCR- and BCR-mediated signals, and to bind certain pathogen-associated molecular patterns. These findings position CD5 as an attractive target for developing immunotherapies aimed at either boosting or dampening ongoing immune responses. Here the available data on the function of CD5 and its involvement in the regulation of immune responses in health and disease are reviewed, as well as the evidence for and future challenges in developing therapeutic strategies aimed at targeting CD5 for autoimmune diseases, cancer, and infections.

Sepsis still constitutes an unmet clinical need, which could benefit from novel adjunctive strategies to conventional antibiotic therapy. The soluble form of the scavenger-like human CD6 lymphocyte receptor (shCD6) binds to key pathogenic components from Gram-positive and -negative bacteria and shows time- and dose-dependent efficacy in mouse models of monobacterial sepsis. The objective of the present work was to demonstrate the effectiveness of infusing mouse and human sCD6 by different systemic routes, either alone or as adjunctive therapy to gold standard antibiotics, in a lethal model of polymicrobial sepsis. To this end, C57BL/6 mice undergoing high-grade septic shock induced by cecal ligation and puncture (CLP; ≥90% lethality) were infused via the intraperitoneal (i.p.) or intravenous (i.v.) route with shCD6 at different doses and time points, either alone or in combination with imipenem/cilastatin (I/C) at a dose of 33 mg/kg of body weight every 8 h. Significantly reduced mortality and proinflammatory cytokine levels were observed by i.p. infusion of a single shCD6 dose (1.25 mg/kg) 1 h pre- or post-CLP. When using the i.v. route, mice survival was significantly extended by starting shCD6 infusion at later time points post-CLP (up to 6 h after CLP). Significant adjunctive effects on mouse survival were observed by i.p. or i.v. infusion of shCD6 in combination with i.p. I/C post-CLP. Similar results were obtained in mice expressing high sustained levels (5 to 10 μg/ml) of mouse sCD6 in serum by means of transduction with hepatotropic adeno-associated virus (AAV). Taken together, the data support the conserved antibacterial effects of human and mouse sCD6 and their use as adjunctive therapy in experimental models of complex and severe polymicrobial sepsis., This work was supported by grants from the Spanish Ministerio de Economía y Competitividad (Plan Nacional de I+D+i, SAF2013-46151-R), Instituto de Salud Carlos III (ISCIII)-cofinanced by European Development Regional Fund “A way to achieve Europe” ERDF (Spanish Network for Research in Infectious Diseases, REIPI, RD12/0015/0018), and Fundació La Marató TV3 (201319-30-31). F.A. is recipient of a Sara Borrell fellowship (CD15/00016) from ISCIII.

Sepsis still constitutes an unmet clinical need, which could benefit from novel adjunctive strategies to conventional antibiotic therapy. The soluble form of the scavenger-like human CD6 lymphocyte receptor (shCD6) binds to key pathogenic components from Gram-positive and -negative bacteria and shows time- and dose-dependent efficacy in mouse models of monobacterial sepsis. The objective of the present work was to demonstrate the effectiveness of infusing mouse and human sCD6 by different systemic routes, either alone or as adjunctive therapy to gold standard antibiotics, in a lethal model of polymicrobial sepsis. To this end, C57BL/6 mice undergoing high-grade septic shock induced by cecal ligation and puncture (CLP; ≥90% lethality) were infused via the intraperitoneal (i.p.) or intravenous (i.v.) route with shCD6 at different doses and time points, either alone or in combination with imipenem/cilastatin (I/C) at a dose of 33 mg/kg of body weight every 8 h. Significantly reduced mortality and proinflammatory cytokine levels were observed by i.p. infusion of a single shCD6 dose (1.25 mg/kg) 1 h pre- or post-CLP. When using the i.v. route, mice survival was significantly extended by starting shCD6 infusion at later time points post-CLP (up to 6 h after CLP). Significant adjunctive effects on mouse survival were observed by i.p. or i.v. infusion of shCD6 in combination with i.p. I/C post-CLP. Similar results were obtained in mice expressing high sustained levels (5 to 10 μg/ml) of mouse sCD6 in serum by means of transduction with hepatotropic adeno-associated virus (AAV). Taken together, the data support the conserved antibacterial effects of human and mouse sCD6 and their use as adjunctive therapy in experimental models of complex and severe polymicrobial sepsis., This work was supported by grants from the Spanish Ministerio de Economía y Competitividad (Plan Nacional de I+D+i, SAF2013-46151-R), Instituto de Salud Carlos III (ISCIII)-cofinanced by European Development Regional Fund “A way to achieve Europe” ERDF (Spanish Network for Research in Infectious Diseases, REIPI, RD12/0015/0018), and Fundació La Marató TV3 (201319-30-31). F.A. is recipient of a Sara Borrell fellowship (CD15/00016) from ISCIII.

Scavenger receptors (SRs) are structurally heterogeneous cell surface receptors characterized by their capacity to remove extraneous or modified self-macromolecules from circulation, thus avoiding the accumulation of noxious agents in the extracellular space. This scavenging activity makes SRs important molecules for host defense and homeostasis. In turn, SRs keep the activation of the steady-state immune response in check, and participate as co-receptors in the priming of the effector immune responses when the macromolecules are associated with a threat that might compromise host homeostasis. Therefore, SRs built up sophisticated sensor mechanisms controlling the immune system, which may be exploited to develop novel drugs for cancer immunotherapy. In this review, we focus on the regulation of the anti-tumor immune response by two paradigmatic SRs: the lymphocyte receptor CD5 and the more broadly distributed scavenger receptor class B type 1 (SR-B1). Cancer immunity can be boosted by blockade of SRs working as immune checkpoint inhibitors (CD5) and/or by proper engagement of SRs working as innate danger receptor (SR-B1). Thus, these receptors illustrate both the complexity of targeting SRs in cancer immunotherapy and also the opportunities offered by such an approach.

Gram-positive bacteria cause a broad spectrum of infection-related diseases in both immunocompetent and immunocompromised hosts, ranging from localized infections to severe systemic conditions such as septic and toxic shock syndromes. This situation has been aggravated by the recent emergence of multidrug-resistant strains, thus stressing the need for alternative therapeutic approaches. One such possibility would be modulating the host's immune response. Herein, the potential use of a soluble form of the scavenger-like human lymphocyte receptor CD6 (shCD6) belonging to an ancient family of innate immune receptors has been evaluated. shCD6 can bind to a broad spectrum of gram-positive bacteria thanks to the recognition of highly conserved cell wall components (lipoteichoic acid [LTA] and peptidoglycan [PGN]), which are essential for their viability and pathogenicity and are not amenable to antibiotic resistance. shCD6 has in vitro inhibitory effects on both bacterial growth and Toll-like receptor-mediated inflammatory response induced by LTA plus PGN. In vivo infusion of shCD6 improves survival on mouse models of septic shock by Staphylococcus aureus (either multidrug-resistant or -sensitive) or their endotoxins (LTA + PGN) or exotoxins (TSST-1). These results support the use of shCD6 and/or other scavenger-like immune receptors in the treatment of severe gram-positive-induced infectious conditions.

Orta-Mascaró et al., The CD6 glycoprotein is a lymphocyte surface receptor putatively involved in T cell development and activation. CD6 facilitates adhesion between T cells and antigen-presenting cells through its interaction with CD166/ALC AM (activated leukocyte cell adhesion molecule), and physically associates with the T cell receptor (TCR) at the center of the immunological synapse. However, its precise role during thymocyte development and peripheral T cell immune responses remains to be defined. Here, we analyze the in vivo consequences of CD6 deficiency. CD6-/- thymi showed a reduction in both CD4 and CD8 single-positive subsets, and double-positive thymocytes exhibited increased Ca2 mobilization to TCR cross-linking in vitro. Bone marrow chimera experiments revealed a T cell-autonomous selective disadvantage of CD6-/- T cells during development. The analysis of TCR-transgenic mice (OT-I and Marilyn) confirmed that abnormal T cell selection events occur in the absence of CD6. CD6-/- mice displayed increased frequencies of antigen-experienced peripheral T cells generated under certain levels of TCR signal strength or co-stimulation, such as effector/memory (CD4TEM and CD8TCM) and regulatory (T reg) T cells. The suppressive activity of CD6-/- T reg cells was diminished, and CD6-/- mice presented an exacerbated autoimmune response to collagen. Collectively, these data indicate that CD6 modulates the threshold for thymocyte selection and the generation and/or function of several peripheral T cell subpopulations, including T reg cells., This work is supported by grants from: Worldwide Cancer Research (14-1275) and Fundació La Marató TV3 (201319-30) to F. Lozano; Spanish Ministerio de Economía y Competitividad (Plan Nacional I+D+i) co-financed by European Development Regional Fund “A way to achieve Europe” to F. Lozano (SAF2013-46151-R), J. Merino (SAF2012-34059), R. Merino (SAF2014-55088-R), and R. Vicente (SAF2014- 52228-R); IPT2011-1527-010000 (associated to Fibrostatin SL) to J. Merino; and Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, European Research Council (FP7/2007–2013 grant no. 322465), and ANR grant Basilic to B. Malissen and M. Malissen. M. Orta-Mascaró, I. Simões, and E. Carreras are recipients of fellowships from Ministerio de Economía y Competitividad (BES-2011-048415), Fundação para a Ciência e a Tecnologia (SFRH/ BD/75738/2011), and European Community Seventh Framework Program (BIOTRACK, FP7/2007/2013;229673), respectively. National Institutes of Health grants to Velocigene at Regeneron Inc. (U01HG004085), and the CSD Consortium (U01HG004080) funded the generation of gene-targeted vectors and ES cells for 8,500 genes in the KOMP Program and archived and distributed by the KOMP Repository at UC Davis and CHORI (U42RR024244).

CD6 is a lymphocyte glycoprotein receptor that physically associates with the antigen-specific receptor complex at the center of the immunological synapse, where it interacts with its ligand CD166/ALCAM. The present work reports the carbohydrate-dependent interaction of CD6 and CD166/ALCAM with Galectin-1 and -3, two well-known soluble mammalian lectins. Both galectins interfered with superantigen-induced T cell proliferation and cell adhesion phenomena mediated by the CD6-CD166/ALCAM pair, while CD6 expression protected cells from galectin-induced apoptosis. The results suggest that interaction of Galectin-1 and -3 with CD6 and CD166/ALCAM might modulate some relevant aspects of T cell physiology.