title: 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.
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto.
authors.forename: Diego L
authors.initials: DL
authors.lastname: Costa
authors.affiliation: Immunology Service, University Hospital Professor Edgar Santos, Federal University of Bahia National Institute of Science and Technology in Tropical Diseases (INCT-DT), Salvador, Brazil.
authors.forename: Tiago M
authors.initials: TM
authors.lastname: Cardoso
authors.affiliation: Immunology Service, University Hospital Professor Edgar Santos, Federal University of Bahia National Institute of Science and Technology in Tropical Diseases (INCT-DT), Salvador, Brazil.
authors.forename: Adriano
authors.initials: A
authors.lastname: Queiroz
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto.
authors.forename: Cristiane M
authors.initials: CM
authors.lastname: Milanezi
authors.affiliation: Immunology Service, University Hospital Professor Edgar Santos, Federal University of Bahia National Institute of Science and Technology in Tropical Diseases (INCT-DT), Salvador, Brazil.
authors.forename: Olívia
authors.initials: O
authors.lastname: Bacellar
authors.affiliation: Immunology Service, University Hospital Professor Edgar Santos, Federal University of Bahia National Institute of Science and Technology in Tropical Diseases (INCT-DT), Salvador, Brazil.
authors.forename: Edgar M
authors.initials: EM
authors.lastname: Carvalho
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto.
authors.forename: João S
authors.initials: JS
authors.lastname: Silva
mesh_terms: D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D053699:Interleukin-7 Receptor alpha Subunit / Q000032:analysis; D007378:Interleukins / Q000096:biosynthesis; D007892:Leishmania braziliensis / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology*; D055815:Young Adult; D000098546:Interleukin-21
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508609:IL10 protein, human; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D007378:Interleukins; C464565:MYDGF protein, human; D016753:Interleukin-10; D007371:Interferon-gamma; D000098546:Interleukin-21
keywords: IL-10; L. braziliensis; Tr-1 cells; tegumentary leishmaniasis