Fenutría, RafaelMartinez, Vanesa GabrielaSimões, InêsPostigo, JorgeGil, VictorMartínez-Florensa, MarioSintes, JordiNaves, RodrigoCashman, Kevin S.Alberola-Ila, JoséRamos Casals, ManuelSoldevila, GloriaRaman, ChanderMerino, JesúsMerino, RamónEngel Rocamora, PabloLozano Soto, Francisco2017-07-032017-07-032014-01-151932-6203https://hdl.handle.net/2445/113245CD5 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.15 p.application/pdfengcc-by (c) Fenutría, Rafael et al., 2014http://creativecommons.org/licenses/by/3.0/esCèl·lules BCèl·lules TLimfòcitsAntígensMelsaResposta immunitàriaB cellsT cellsLymphocytesAntigensSpleenImmune responseinfo:eu-repo/semantics/article6473872017-07-03info:eu-repo/semantics/openAccess24454761