A potential side effect of cyclosporin A:: Inhibition of CD4+CD25+ regulatory T cells in mice

Background. CD4(+) CD25(+) regulatory T (Treg) cells are essential for the induction and maintenance of immunologic self-tolerance as well as transplant tolerance. The effects of cyclosporin A (CsA), a widely used immunosuppressive agent, on CD4(+)CD25(+)Treg cells in mice were investigated. Methods. Balb/c mice were injected with CsA or control solution for one month. The levels, phenotype, and function of CD4(+)CD25(+)Treg cells in these mice were then assayed. Results. The percentages and total cell numbers of CD4(+)CD25(+)Treg cells in the peripheral blood and spleen were significantly reduced after the treatment with CsA. The total numbers of CD4(+)CD25(+)Treg cells in the thymus of CsA-treated mice were markedly reduced as compared to the control mice. However, the percentage of CD4(+)CD25(+)Treg cells in the thymus of CsA-treated mice was markedly enhanced. More CD4(+)CD25(+)Treg cells expressing high levels of CD44 and CD45RB, and less CD4(+)CD25(+)Treg cells expressing CD62L were observed in CsA-treated mice, compared with the control mice. CD4(+)CD25(+)Treg cells expressed slightly lower levels of Foxp3 in CsA-treated mice. Furthermore, CsA markedly impaired the immunosuppressive function of CD4(+)CD25(+)Treg cells. Conclusions. CsA significantly impaired the development and function of CD4(+)CD25(+)Treg cells. The present studies suggest that CsA may block the potential induction of immune tolerance and increase the susceptibility to develop autoimmune diseases while preventing graft rejection.