Differential immune regulation of activated T cells between cutaneous and mucosal leishmaniasis as a model for pathogenesis

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Abstract
SUMMARY: Cutaneous (CL) and mucosal leishmaniasis (ML) are characterized by a predominant type 1 immune response (IFN‐γ and TNF‐α production) and strong inflammatory response in the lesions with few parasites. This exacerbated type 1 response is more evident in ML as compared to CL. Our main hypothesis is that a differential immune regulation of T cell activation leads to over reactive T cells in ML. In the present study, we investigated immunological factors that could explain the mechanisms behind it by comparing some immune regulatory mechanisms between ML and CL patients: frequency of cells expressing co‐stimulatory molecules, apoptotic markers, T cell activation markers; and ability of neutralizing antibodies to IL‐2, IL‐12 and IL‐15 do down‐regulate IFN‐γ production in leishmania antigen‐stimulated peripheral blood mononuclear cells (PBMC). Interestingly, in CL anti‐IL‐2 and anti‐IL‐15 significantly suppressed antigen‐specific IFN‐γ production, while in ML only anti‐IL‐2 suppressed IFN‐γ production. Finally, higher frequency of CD4+ T cells expressing CD28−, CD69+ and CD62L low were observed in ML as compared to CL. These data indicate that an exacerbated type 1 response in ML is differentially regulated and not appropriately down modulated, with increased frequencies of activated effectors T cells, maintaining the persistent inflammatory response and tissue damage observed in ML.

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