Functional and therapeutical implications of ligand recognition by the scavenger-like lymphocyte receptors CD5 and CD6

Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina

The CD5 and CD6 lymphocyte surface receptors are highly homologous members of the Scavenger Receptor Cystein Rich (SRCR) superfamily mainly expressed by all T lymphocytes and the B1a subpopulation of B cells. Although the ultimate function/s are far from being completely understood, CD5 and CD6 are known to play a relevant role in both lymphocyte development and differentiation by negatively modulating the survival/death-inducing intracellular signals generated during the antigen recognition. Recently, this group has developed a transgenic mouse line which expresses a soluble form of human CD5, likely blocking the ligand-receptor interactions mediated by CD5 and interfering with normal lymphocyte response. This study was aimed at furthering the study of the recombinant soluble human CD5 Transgenic(rshCD5Tg) mouse phenotypical analysis, its response to antigen stimuli and tumor implantation; the function of rshCD6 was also tested. It was observed that rshCD5Tg mice display an exacerbated immune response, likely due to a reduction in the number of T and B cells with regulatory/suppressive function (Treg, B1a, B10 cells) and the increase in effector cells (NKT, MZ B cells). In agreement with these phenotypical characteristics, the functional analysis of rshCD5Tg mice showed enhanced immune responses to Tdependent and –independent antigens, as well as enhanced anti-tumoral responses, with or without concomitant chemotherapy treatment. Importantly, both the phenotypical and functional findings could be reproduced in wild-type mice following prolonged infusion of purified exogenous rshCD5 protein. Overall, these results argue in favor of a relevant role of CD5-mediated molecular interactions in the homeostasis of functionally relevant lymphocyte subpopulations and open the possibility for CD5-based therapeutical interventions in different disease settings such as cancer, infection and immunodeficiency.