Title:
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Transgenic expression of soluble human CD5 enhances experimentally-induced autoimmune and anti-tumoral immune responses
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Author:
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Fenutría, Rafael; Martinez, Vanesa G.; Simões, Inês; Postigo, Jorge; Gil, Victor; Martinez-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
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Other authors:
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Universitat de Barcelona |
Abstract:
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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. |
Subject(s):
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-Cèl·lules B -Cèl·lules T -Limfòcits -Antígens -Melsa -Resposta immunitària -B cells -T cells -Lymphocytes -Antigens -Spleen -Immune response |
Rights:
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cc-by (c) Fenutría, Rafael et al., 2014
http://creativecommons.org/licenses/by/3.0/es |
Document type:
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Article Article - Published version |
Published by:
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Public Library of Science (PLoS)
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