CD4(+) CD25(+) T cells in skin lesions of patients with cutaneous leishmaniasis exhibit phenotypic and functional characteristics of natural regulatory T cells

Abstract

Endogenous regulatory T ( T-reg) cells are involved in the control of infections, including Leishmania infection in mice. Leishmania viannia braziliensis is the main etiologic agent of cutaneous leishmaniasis ( CL) in Brazil, and it is also responsible for the more severe mucocutaneous form. Here, we investigated the possible involvement of T-reg cells in the control of the immune response in human skin lesions caused by L. viannia braziliensis infection. We show that functional T-reg cells can be found in skin lesions of patients with CL. These cells express phenotypic markers of T-reg cells-such as CD25, cytotoxic T lymphocyte-associated antigen 4, Foxp3, and glucocorticoid-induced tumor necrosis factor receptor-and are able to produce large amounts of interleukin-10 and transforming growth factor-beta. Furthermore, CD4(+) CD25(+) T cells derived from the skin lesions of 4 of 6 patients with CL significantly suppressed in vitro the phytohemagglutinin-induced proliferative T cell responses of allogeneic peripheral-blood mononuclear cells ( PBMCs) from healthy control subjects at a ratio of 1 T-reg cell to 10 allogeneic PBMCs. These findings suggest that functional Treg cells accumulate at sites of Leishmania infection in humans and possibly contribute to the local control of effector T cell functions.