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Title: | Transgenic expression of soluble human CD5 enhances experimentally-induced autoimmune and anti-tumoral immune responses |
Author: | 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 |
Keywords: | Cèl·lules B Cèl·lules T Limfòcits Antígens Melsa Resposta immunitària B cells T cells Lymphocytes Antigens Spleen Immune response |
Issue Date: | 15-Jan-2014 |
Publisher: | Public Library of Science (PLoS) |
Abstract: | 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0084895 |
It is part of: | PLoS One, 2014, vol. 9, num. 1, p. e84895 |
URI: | http://hdl.handle.net/2445/113245 |
Related resource: | https://doi.org/10.1371/journal.pone.0084895 |
ISSN: | 1932-6203 |
Appears in Collections: | Articles publicats en revistes (Medicina) Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Biomedicina) |
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