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

Abstract

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 peripheral blood mononuclear cells (PBMCs) from patients with cutaneous leishmaniasis due to Leishmania braziliensis are CD4(+)CD25(-)CD127(-/low)FOXP3(-) 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 production 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.

Interleukin-27 Early Impacts Leishmania infantum Infection in Mice and Correlates with Active Visceral Disease in Humans

“…are expert in modulating immune activity through diverse strategies (4). Previous reports on human leishmaniasis indicate that IL-27 increases when the disease is active in both cutaneous (26–28) and visceral forms (7, 8). Here, for the first time, plasma levels of IL-27 were evaluated in L. infantum -infected individuals from Europe.…”

Evaluation of Regulatory Immune Response in Skin Lesions of Patients Affected by Nonulcerated or Atypical Cutaneous Leishmaniasis in Honduras, Central America

“…The lack of correlation between FoxP3 + and IL-10 + cells suggests that other regulatory cells could be the source of IL-10, since it has been described that IL-10-producing CD25 − Foxp3 − T cells are involved in the pathogenesis of visceral leishmaniasis [ 27 ]. Moreover, skin lesions of patients affected by cutaneous leishmaniasis caused by L. (V.) braziliensis showed a stronger correlation between IL-10 expression and proinflammatory cytokines such as IFN- γ , IL-27, and IL-21, rather than with FoxP3 + cells [ 28 ].…”

Development of real-time PCR assays for evaluation of immune response and parasite load in golden hamster (Mesocricetus auratus) infected by Leishmania (Viannia) braziliensis

“…Thus, the nature of the CD4 + T cell response during active CL and through disease resolution is associated with robust production of inflammatory cytokines, such as TNF and IFN-γ, even in the presence of IL-10, a regulatory cytokine that acts to reduce the production of TNF [ 32 ]. In patients with cutaneous leishmaniasis derived from L. braziliensis infection, production of IFN-γ and IL-10 was detected in the skin lesions [ 33 ]. It is possible that CD4 + CD25 + IL-10 + TGF-β + T cells are involved in the modulation of the effector immune response in the skin lesions induced by Leishmania infection in humans.…”