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Transgenic expression of soluble human CD5 enhances experimentally-induced autoimmune and anti-tumoral immune responses Fenutría, Rafael Martinez, Vanesa Gabriela Simões, Inês Postigo, Jorge Gil, Victor Martínez-Florensa, Mario Sintes, Jordi Naves, Rodrigo Cashman, Kevin S. Alberola-Ila, José Ramos Casals, Manuel Soldevila, Gloria Raman, Chander Merino, Jesús Merino, Ramón Engel Rocamora, Pablo Lozano Soto, Francisco Cèl·lules B Cèl·lules T Limfòcits Antígens Melsa Resposta immunitària B cells T cells Lymphocytes Antigens Spleen Immune response CD5 is a lymphoid-specific transmembrane glycoprotein constitutively expressed on thymocytes and mature T and B1a lymphocytes. Current data support the view that CD5 is a negative regulator of antigen-specific receptor-mediated signaling in these cells, and that this would likely be achieved through interaction with CD5 ligand/s (CD5L) of still undefined nature expressed on immune or accessory cells. To determine the functional consequence of loss of CD5/CD5L interaction in vivo, a new transgenic mouse line was generated (shCD5EμTg), expressing a circulating soluble form of human CD5 (shCD5) as a decoy to impair membrane-bound CD5 function. These shCD5EμTg mice showed an enhanced response to autologous antigens, as deduced from the presentation of more severe forms of experimentally inducible autoimmune disease (collagen-induced arthritis, CIA; and experimental autoimmune encephalitis, EAE), as well as an increased anti-tumoral response in non-orthotopic cancer models (B16 melanoma). This enhancement of the immune response was in agreement with the finding of significantly reduced proportions of spleen and lymph node Treg cells (CD4+CD25+FoxP3+), and of peritoneal IL-10-producing and CD5+ B cells, as well as an increased proportion of spleen NKT cells in shCD5EμTg mice. Similar changes in lymphocyte subpopulations were observed in wild-type mice following repeated administration of exogenous recombinant shCD5 protein. These data reveal the relevant role played by CD5/CD5L interactions on the homeostasis of some functionally relevant lymphocyte subpopulations and the modulation of immune responses to autologous antigens. 2017-07-03T11:23:15Z 2017-07-03T11:23:15Z 2014-01-15 2017-07-03T11:23:15Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0084895 PLoS One, 2014, vol. 9, num. 1, p. e84895 https://doi.org/10.1371/journal.pone.0084895 cc-by (c) Fenutría, Rafael et al., 2014 http://creativecommons.org/licenses/by/3.0/es info:eu-repo/semantics/openAccess Public Library of Science (PLoS) Articles publicats en revistes (Biomedicina)