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

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.Univ São Paulo, Sch Med Ribeirao Preto, Dept Biochem & Immunol, BR-14049900 Ribeirao Preto, SP, BrazilUniv São Paulo, Sch Med Ribeirao Preto, Div Dermatol, BR-14049900 Ribeirao Preto, SP, BrazilUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, BrazilGoncalo Moniz Res Inst, Fortaleza, Ceara, BrazilInst Invest Immunol, Fortaleza, Ceara, BrazilCtr Dermatol Dona Libana, Fortaleza, Ceara, BrazilNIH, Mucosal Immunol Unit, Parasit Dis Lab, Bethesda, MD 20892 USAUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, BrazilWeb of Scienc