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Transgenic Expression of Soluble Human CD5 Enhances Experimentally-Induced Autoimmune and Anti-Tumoral Immune Responses

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.

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Fuente: PLoS One. 2014 Jan 15;9(1):e84895

Editorial: Public Library of Science

 Fecha de publicación: 15/01/2014

Nº de páginas: 15

Tipo de publicación: Artículo de Revista

DOI: 10.1371/journal.pone.0084895

ISSN: 1932-6203

Autores/as

FENUTRÍA, RAFAEL

MARTÍNEZ, VANESA G.

SIMÕES, INES

JORGE POSTIGO FERNANDEZ

GIL ESPINOSA, VÍCTOR

MARTÍNEZ FLORENSA, MARIO

SINTES, JORDI

NAVES, RODRIGO

CASHMAN, KEVIN S.

ALBEROLA ILA, JOSÉ

RAMOS CASALS, MANEL

SOLDEVILA MELGAREJO, GLORIA

RAMAN, CHANDER

ENGEL ROCAMORA, PABLO

LOZANO SOTO, FRANCISCO