CD5 plays an inhibitory role in the suppressive function of murine CD4⁺ CD25⁺ T_reg cells

A subset of CD4⁺ T cells, the CD4⁺ CD25⁺ regulatory T (T_reg) cells in the lymphoid organs and peripheral blood are known to possess suppressive function. Previous in vitro and in vivo studies have indicated that T cell receptor (TCR) signal is required for development of such 'natural regulatory (T_reg) cells' and for activation of the effector function of CD4⁺ CD25⁺ regulatory T cells. CD5 is a cell surface molecule present on all T cells and a subtype of B lymphocytes, the B-1 cells, primarily localized to coelomic cavities, Peyer's patches, tonsils and spleen. CD5 acts as a negative regulator of T cell and B cell signaling via recruitment of SHP-1. Here, we demonstrate that T_reg cells obtained from CD5^-/- mice are more potent than those from wild type mice in suppressing the in vitro cell proliferation of anti-CD3 stimulated CD4⁺ CD25^- responder T cells. This phenomenon was cell contact and GITR dependent. Lack of CD5 expression on T_reg cells (from spleen, lymph node and thymus) did not affect the intracellular levels of Foxp3. However, CD5^-/- T_reg thymocytes were able to elicit a higher Ca²⁺ response to TCR + co-stimulatory signals than the wild type cells. CD5^-/- mice expressed more Foxp3 mRNA in the colon than wild type mice, and additionally, the severity of the dextran sulfate sodium (DSS)-induced colitis in CD5^-/- mice was less than the wild type strain. We suggest that manipulation of CD5 expression or the downstream signaling components of CD4⁺ CD25⁺ T_reg cells as a potential strategy for therapeutic intervention in cases of auto-immune disorders.