Transgenic expression of soluble human CD5 enhances experimentally-induced autoimmune and anti-tumoral immune responses. Transgenic expression of soluble human CD5 enhances experimentally-induced autoimmune and anti-tumoral immune responses. R. Fenutrıa, VG. Martinez, I. Simoẽs, J. Postigo, V. Gil, M. Martínez-Florensa, J. Sintes, R. Naves, KS. Cashman, J. Alberola-Ila, M. Ramos-Casals, G. Soldevila, C. Raman, J. Merino, R. Merino, P. Engel and F. Lozano. 2014-01-14T23:00:00Z<p>​<strong class="ms-rteFontSize-2" style="text-align:justify;">Abstract:</strong></p><p style="text-align:justify;"><span class="ms-rteFontSize-2">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 antitumoral 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.</span><br></p><p><span class="ms-rteFontSize-2"></span></p><p><span class="ms-rteFontSize-2"><a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0084895">​PLoS ONE, 2014, 9: e84895. DOI: 10.1371/journal.pone.0084895.</a></span></p>161