Chemokine receptors on human regulatory T cells during cutaneous leishmaniasis

Abstract

The aim of this work was to define the population of regulatory T cells (Tregs) which are circulating in the blood of Leishmania infected individuals clinically displaying a lesion (active disease–AD) and sub‐clinical (SC) ones. We have individually collected blood samples, processed the PBMC and stained with fluorochrome‐conjugated antibodies against CD3, CD4, Foxp3, CD25, CTLA‐4, Ki‐67, CCR4, CCR5, and CCR7. Cells were analyzed by flow cytometry. Our results suggest that CD25 and CTLA‐4 are upregulated in Tregs of AD patients when compared to SC and uninfected (UN) controls. Moreover, Tregs proliferate upon infection based on Ki‐67 nuclear antigen staining. Finally, we have observed that these Tregs of SC and AD patients upregulate CCR4, but not CCR5 and CCR7. There is an increase in the number of circulating Tregs in the blood of Leishmania infected individuals. These cells are potentially more suppressive based on the increased upregulation of CD25 and CTLA‐4 during clinical infection (AD) when compared to SC infection. Tregs of both SC and AD cohorts are proliferating and express CCR4, which potentially guide them to the skin, but do not upregulate CCR5 and CCR7.

Antigen recognition reinforces regulatory T cell mediated Leishmania major persistence

“…Importantly, Treg-mediated suppression was not dependent on tissue source (isolated from healed skin vs lymph node of naïve mice) and were equally expanded and suppressive following L. major infection 17 . Regulatory T cells from human lesions displayed higher CCR5 expression, which corresponded with observations that CCR5-deficient mice can completely clear Leishmania major infection 48 , 49 . In a model where galectin-3 deficiency increases the frequency of peripheral Tregs, the severity and parasite burden following L. major infection was increased significantly 50 .…”