@article{10902/4252,
year = {2014},
month = {1},
url = {http://hdl.handle.net/10902/4252},
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.},
organization = {This study was supported by grants from the Spanish Ministerio de Economía y Competitividad [Plan Nacional de I+D+i, SAF2010-19717], Generalitat de Catalunya [2009SGR1101], and Instituto de Salud Carlos III [Spanish Network for Research in Infectious Diseases, REIPI RD12/0015/0018] to FL, from Spanish Ministerio de Economía y Competitividad [SAF2011-22463], co-funded by the European Regional Development Fund, to RM, from Ministerio de Economía y Competitividad [SAF2012-34059], co-funded by the European Regional Development Fund, and the Spanish Ministerio de Economía y Competitividad (IPT2011-1527-010000) associated to Fibrostatin SL, to JM, and from NIH AI1076562 and National Multiple Sclerosis Society RG3891 to CR. MM-F and VGM are recipients of fellowships from Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) of the Generalitat de Catalunya [2010TEM37] and from Spanish Ministerio de Economía y Competitividad [JCI-2010-06378], respectively. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.},
publisher = {Public Library of Science},
publisher = {PLoS One, 2014, 9(1), e84895},
title = {Transgenic Expression of Soluble Human CD5 Enhances Experimentally-Induced Autoimmune and Anti-Tumoral Immune Responses},
author = {Fenutría, Rafael and Martínez, Vanesa G. and Simoes, Ines and Postigo Fernández, Jorge and Gil Espinosa, Víctor and Martínez Florensa, Mario and Sintes, Jordi and Naves, Rodrigo and Cashman, Kevin S. and Alberola Ila, José and Ramos Casals, Manel and Soldevila Melgarejo, Gloria and Raman, Chander and Merino Pérez, Jesús and Merino Pérez, Ramón and Engel Rocamora, Pablo and Lozano Soto, Francisco},
}