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 (Treg) 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 Treg cells in the control of the immune response in human skin lesions caused by L. viannia braziliensis infection. We show that functional Treg cells can be found in skin lesions of patients with CL. These cells express phenotypic markers of Treg 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 Treg 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.

Intralesional Regulatory T-Cell Suppressive Function during Human Acute and Chronic Cutaneous Leishmaniasis Due to Leishmania guyanensis

“…However, in these experiments, the level of Treg cells was not evaluated in control subjects, and the number of Treg cells within lesions was not determined (28). In another study, the accumulation of Treg cells with suppressive activity was described for lesions of patients suffering from leishmaniasis due to L. braziliensis (10), confirming that Treg cells are present predominantly at the site of infection during infection with Leishmania.…”

“…Treg cells with immunosuppressive functions have been identified clearly in skin lesions from patients infected with L. braziliensis, but their exact role in pathogenesis has not been evaluated (10). More recently, Treg cells have also been identified in peripheral blood mononuclear cells (PBMC) from acute and cured localized cutaneous leishmaniasis patients infected with L. braziliensis (28).…”

Phenotypic analysis of human peripheral blood regulatory T cells (CD4+FOXP3+CD127lo/–) ex vivo and after in vitro restimulation with malaria antigens

“…Treg can be found in peripheral blood, lymph nodes [11][12][13][14][15][16], non-lymphoid tissues and at sites of infection [17][18][19][20][21][22][23][24][25]. In mice, Treg have been shown to migrate to different locations according to their patterns of chemokine receptor (CCR) expression.…”

Immunological Determinants of Clinical Outcome in Peruvian Patients with Tegumentary Leishmaniasis Treated with Pentavalent Antimonials

“…A defect in IL-10 receptor expression was shown to correlate with high inflammatory responses in ML (14). Finally, T reg cells and high IL-10 production potential have been described in the skin of individuals infected with L. braziliensis (10).…”