Tr-1-Like CD4(+)CD25(-)CD127(-/low)FOXP3(-) Cells Are the Main Source of Interleukin 10 in Patients With Cutaneous Leishmaniasis Due to Leishmania braziliensis

Author(s)

Costa, Diego L. ^[1] ; Cardoso, Tiago M. ^{[2, 3]} ; Queiroz, Adriano ^{[2, 3]} ; Milanezi, Cristiane M. ^[1] ; Bacellar, Olivia ^{[2, 3]} ; Carvalho, Edgar M. ^{[2, 3]} ; Silva, Joao S. ^[1]

Affiliation

^[1] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Biochem & Immunol, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Fed Bahia, Immunol Serv, Univ Hosp Prof Edgar Santos, Salvador, BA - Brazil

^[3] Natl Inst Sci & Technol Trop Dis INCT DT, Salvador, BA - Brazil

• Document type: Journal article
• Source: Journal of Infectious Diseases; v. 211, n. 5, p. 708-718, MAR 1 2015.
• Web of Science Citations: 10

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 alpha 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. expression, rather than with FOXP3 or transforming growth factor beta expressions. Active production of both interleukin 27 and interleukin 21, together with production of interferon gamma 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. (AU)

• FAPESP's process: 08/05982-8 - Modulation of immune responses to Leishmania braziliensis by regulatory T cells
• Grantee: Diego Luís Costa
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 07/53940-0 - The regulatory T cells and TH17 in the immune response against infections, tumors and autoimmune diseases
• Grantee: João Santana da Silva
• Support Opportunities: Research Projects - Thematic Grants