Relevance of CD6-Mediated interactions in the regulation of peripheral T-Cell responses and tolerance

The CD6 lymphocyte receptor has been involved in the pathophysiology of different autoimmune disorders and is now considered a feasible target for their treatment. In vitro data show the relevance of CD6 in the stabilization of adhesive contacts between T-cell and antigen-presenting cells, and the m...

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Autores: Consuegra-Fernández, Marta, Martínez-Florensa, Mario, Aranda, Fernando, Salort, José de, Armiger Borràs, Noelia, Lozano, Teresa, Casares, Noelia, José Lasarte, Juan, Engel Rocamora, Pablo, Lozano Soto, Francisco
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/138817
Acesso em linha:https://hdl.handle.net/2445/138817
Access Level:acceso abierto
Palavra-chave:Cèl·lules T
Biologia molecular
Receptors cel·lulars
T cells
Molecular biology
Cell receptors
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spelling Relevance of CD6-Mediated interactions in the regulation of peripheral T-Cell responses and toleranceConsuegra-Fernández, MartaMartínez-Florensa, MarioAranda, FernandoSalort, José deArmiger Borràs, NoeliaLozano, TeresaCasares, NoeliaJosé Lasarte, JuanEngel Rocamora, PabloLozano Soto, FranciscoCèl·lules TBiologia molecularReceptors cel·lularsT cellsMolecular biologyCell receptorsThe CD6 lymphocyte receptor has been involved in the pathophysiology of different autoimmune disorders and is now considered a feasible target for their treatment. In vitro data show the relevance of CD6 in the stabilization of adhesive contacts between T-cell and antigen-presenting cells, and the modulation of T-cell receptor signals. However, the in vivo consequences of such a function are yet undisclosed due to the lack of suitable genetically modified animal models. Here, the in vitro and in vivo challenge of CD6-deficient (CD6(-/-)) cells with allogeneic cells was used as an approach to explore the role of CD6 in immune responses under relative physiological stimulatory conditions. Mixed lymphocyte reaction (MLR) assays showed lower proliferative responses of splenocytes from CD6(-/-)mice together with higher induction of regulatory T cells (T-reg, CD4(+)CD25(+)FoxP3(+)) with low suppressive activity on T and B-cell proliferation. In line with these results, CD6(-/-)mice undergoing a lupus-like disorder induced by chronic graft-versus-host disease (cGvHD) showed higher serum titers of anti-double-stranded DNA and nucleosome autoantibodies. This occurred together with reduced splenomegaly, which was associated with lower in vivo bromodesoxyuridine incorporation of spleen cells and with increased percentages of spleen follicular B cells (B2, CD21(+)CD23(hi)) and T-reg cells. Interestingly, functional analysis of in vivo-generated CD6(-/-)T(reg) cells exhibited defective suppressive activity. In conclusion, the data from MLR and cGvHD-induced lupus-like models in CD6(-/-)mice illustrate the relevance of CD6 in T (and B) cell proliferative responses and, even more importantly, Treg induction and suppressive function in the in vivo maintenance of peripheral tolerance.Frontiers Media2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/138817Articles publicats en revistes (Biomedicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.3389/fimmu.2017.00594Frontiers in Immunology, 2017, vol. 8, num. 594https://doi.org/10.3389/fimmu.2017.00594cc-by (c) Consuegra Fernández, Marta et al., 2017http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1388172026-05-27T06:46:51Z
dc.title.none.fl_str_mv Relevance of CD6-Mediated interactions in the regulation of peripheral T-Cell responses and tolerance
title Relevance of CD6-Mediated interactions in the regulation of peripheral T-Cell responses and tolerance
spellingShingle Relevance of CD6-Mediated interactions in the regulation of peripheral T-Cell responses and tolerance
Consuegra-Fernández, Marta
Cèl·lules T
Biologia molecular
Receptors cel·lulars
T cells
Molecular biology
Cell receptors
title_short Relevance of CD6-Mediated interactions in the regulation of peripheral T-Cell responses and tolerance
title_full Relevance of CD6-Mediated interactions in the regulation of peripheral T-Cell responses and tolerance
title_fullStr Relevance of CD6-Mediated interactions in the regulation of peripheral T-Cell responses and tolerance
title_full_unstemmed Relevance of CD6-Mediated interactions in the regulation of peripheral T-Cell responses and tolerance
title_sort Relevance of CD6-Mediated interactions in the regulation of peripheral T-Cell responses and tolerance
dc.creator.none.fl_str_mv Consuegra-Fernández, Marta
Martínez-Florensa, Mario
Aranda, Fernando
Salort, José de
Armiger Borràs, Noelia
Lozano, Teresa
Casares, Noelia
José Lasarte, Juan
Engel Rocamora, Pablo
Lozano Soto, Francisco
author Consuegra-Fernández, Marta
author_facet Consuegra-Fernández, Marta
Martínez-Florensa, Mario
Aranda, Fernando
Salort, José de
Armiger Borràs, Noelia
Lozano, Teresa
Casares, Noelia
José Lasarte, Juan
Engel Rocamora, Pablo
Lozano Soto, Francisco
author_role author
author2 Martínez-Florensa, Mario
Aranda, Fernando
Salort, José de
Armiger Borràs, Noelia
Lozano, Teresa
Casares, Noelia
José Lasarte, Juan
Engel Rocamora, Pablo
Lozano Soto, Francisco
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cèl·lules T
Biologia molecular
Receptors cel·lulars
T cells
Molecular biology
Cell receptors
topic Cèl·lules T
Biologia molecular
Receptors cel·lulars
T cells
Molecular biology
Cell receptors
description The CD6 lymphocyte receptor has been involved in the pathophysiology of different autoimmune disorders and is now considered a feasible target for their treatment. In vitro data show the relevance of CD6 in the stabilization of adhesive contacts between T-cell and antigen-presenting cells, and the modulation of T-cell receptor signals. However, the in vivo consequences of such a function are yet undisclosed due to the lack of suitable genetically modified animal models. Here, the in vitro and in vivo challenge of CD6-deficient (CD6(-/-)) cells with allogeneic cells was used as an approach to explore the role of CD6 in immune responses under relative physiological stimulatory conditions. Mixed lymphocyte reaction (MLR) assays showed lower proliferative responses of splenocytes from CD6(-/-)mice together with higher induction of regulatory T cells (T-reg, CD4(+)CD25(+)FoxP3(+)) with low suppressive activity on T and B-cell proliferation. In line with these results, CD6(-/-)mice undergoing a lupus-like disorder induced by chronic graft-versus-host disease (cGvHD) showed higher serum titers of anti-double-stranded DNA and nucleosome autoantibodies. This occurred together with reduced splenomegaly, which was associated with lower in vivo bromodesoxyuridine incorporation of spleen cells and with increased percentages of spleen follicular B cells (B2, CD21(+)CD23(hi)) and T-reg cells. Interestingly, functional analysis of in vivo-generated CD6(-/-)T(reg) cells exhibited defective suppressive activity. In conclusion, the data from MLR and cGvHD-induced lupus-like models in CD6(-/-)mice illustrate the relevance of CD6 in T (and B) cell proliferative responses and, even more importantly, Treg induction and suppressive function in the in vivo maintenance of peripheral tolerance.
publishDate 2017
dc.date.none.fl_str_mv 2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/138817
url https://hdl.handle.net/2445/138817
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3389/fimmu.2017.00594
Frontiers in Immunology, 2017, vol. 8, num. 594
https://doi.org/10.3389/fimmu.2017.00594
dc.rights.none.fl_str_mv cc-by (c) Consuegra Fernández, Marta et al., 2017
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Consuegra Fernández, Marta et al., 2017
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv Articles publicats en revistes (Biomedicina)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869407942564904960
score 15,301629

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