Arsenic exposure impels CD4 commitment in thymus and suppress T cell cytokine secretion by increasing regulatory T cells

Abstract

Abstract Arsenic is globally infamous for inducing immunosuppression associated with prevalence of opportunistic infection in exposed population, although the mechanism remains elusive. In this study, we investigate the effect of arsenic exposure on thymocyte lineage commitment and the involvement of regulatory T cells (Treg) in arsenic-induced immunosuppression. Male Balb/c mice were exposed to 0.038, 0.38 and 3.8 ppm sodium arsenite for 7, 15 and 30 days through oral gavage. Arsenic exposure promoted CD4 lineage commitment in a dose dependent manner supported by the expression of ThPOK in thymus. Arsenic also increased splenic CD4+ T cells and promoted their differentiation into Treg cells. In parallel, arsenic exposure induced immunosuppression characterized by low cytokine secretion from splenocytes and increased susceptibility to Mycobacterium fortuitum (M. fortuitum) infection. Therefore, we linked arsenic-induced rise in Treg cells with suppressed Th1 and Th2 related cytokines, which has been reversed by inhibition of Treg cells in-vivo using wortmannin. Other parameters like body weight, kidney and liver function, histoanatomy of thymus and spleen as well as thymocyte and splenocytes viability were unaltered by arsenic exposure. Taken together our findings indicated that environmentally relevant dose of arsenic enhanced differentiation of Treg cells which in turn induce immunosuppression in experimental animals.