Tr-1–Like CD4+CD25−CD127−/lowFOXP3 − Cells Are the Main Source of Interleukin 10 in Patients With Cutaneous Leishmaniasis Due to

CD4+CD25+FOXP3+ regulatory T cells have long been shown to mediate susceptibility to Leishmania infection, mainly via interleukin 10 production. In this work, we showed that the main sources of interleukin 10 in pe-ripheral blood mononuclear cells (PBMCs) from patients with cutaneous leishmaniasis due to Leishmania bra-ziliensis are CD4+CD25−CD127−/lowFOXP3 − cells. Compared with uninfected controls, patients with CL had increased frequencies of circulating interleukin 10–producing CD4+CD25−CD127−/low cells, which efficiently suppressed tumor necrosis factor α production by the total PBMC population. Also, in CL lesions, interleukin 10 was mainly produced by CD4+CD25 − cells, and interleukin 10 messenger RNA expression was associated with interleukin 27, interleukin 21, and interferon γ expression, rather than with FOXP3 or transforming growth factor β expressions. Active production of both interleukin 27 and interleukin 21, together with produc-tion of interferon γ and interleukin 10, was also detected in the lesions. Since these cytokines are associated with the differentiation and activity of Tr-1 cells, our results suggest that this cell population may play an important role in the immunomodulation of CL. Therefore, development of treatments that interfere with this pathway may lead to faster parasite elimination. Keywords. L. braziliensis; tegumentary leishmaniasis; Tr-1 cells; IL-10. Upon entrance to the vertebrate host, parasites from th