Characterization of regulatory T cell (Treg) function in patients infected with Leishmania braziliensis

Abstract

Th1 immune responses are crucial for eliminating Leishmania parasites. However, despite strong Th1 responses, cutaneous leishmaniasis (CL) patients infected with L. braziliensis develop the disease, while milder Th1 responses are found in sub-clinical (SC) infections. Therefore, CL patients may experience impaired regulatory T cell (Treg) function, causing excessive Th1 responses and tissue damage. To address this hypothesis, we characterized the function of circulating Tregs in L. braziliensis infected CL patients and compared them to Tregs from uninfected controls (UC) and SC subjects. The frequency of circulating Tregs was similar in CL patients, UC and SC subjects. Moreover, CL patients Tregs suppressed lymphocyte proliferation and PBMC pro-inflammatory cytokine production more efficiently than UC Tregs, and also produced higher levels of IL-10 than UC and SC Tregs. Furthermore, PBMC and mononuclear cells from lesions of CL patients responded normally to Treg-induced suppression. Therefore, the lesion development in CL patients infected with L. braziliensis is not associated with impairment in Treg function or failure of cells to respond to immunomodulation. Rather, the increased Treg activation in CL patients may impair parasite elimination, resulting in establishment of chronic infection. Thus, immunological strategies that interfere with this response may improve leishmaniasis treatment.

The Immunotherapeutic Role of Regulatory T Cells in Leishmania (Viannia) panamensis Infection

“…In patient studies of L. V. panamensis , Treg functionality was diminished during infection but was restored following successful treatment (28). Tregs with varying functionality (with suppressive or non-functional properties) have been identified in lesions of patients infected with L. (V.) braziliensis (24, 25). In contrast for L. (V.) guyanensis (35), although FoxP3 and IDO expression in lesions decrease during disease, higher levels are found for patients with chronic disease, suggesting a role for Tregs in pathogenesis.…”

Regulatory T cells in the actinic cheilitis

“…In order to verify the suppressor activity of Tregs, CD4 + CD25 + T cells (1 × 10 5 cells/well) were first activated as previously described . For Immunosuppression assay, the total PBMC from autologus individuals were stained with CFSE and cultured alone or in presence of CD4 + CD25 + T cells (1 × 10 4 cells/well) with or without 1 μg/ml PHA .…”

“…For each sample, CFSE dilution was evaluated in PHA‐stimulated cultures, in the presence or absence of different amounts of purified CD4 + CD25 + cells. T‐cells proliferation was characterized by sequential halving of CFSE fluorescence, generating equally spaced peaks on a logarithmic scale . Data represent the percentage of inhibition calculated on the PHA‐induced proliferation of allogeneic T cells cultured with PHA in the absence of CD4 + CD25 + T cells.…”

IL2RA Genetic Variants Reduce IL-2–Dependent Responses and Aggravate Human Cutaneous Leishmaniasis

“…Additionally, it could be argued that the effects of the IL2RA variants on CL susceptibility are unrelated to their effects on Treg cells. Previous studies (33,34) have suggested that Treg cells may aggravate L. braziliensis infections. In the Brazilian replication study, rs10905669 did not reach the significance threshold and was not included in the analysis.…”