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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 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
Keywords: Cèl·lules B
Cèl·lules T
Resposta immunitària
B cells
T cells
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.
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It is part of: PLoS One, 2014, vol. 9, num. 1, p. e84895
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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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