Recruitment of CD8+ T cells expressing granzyme A is associated with lesion progression in human cutaneous leishmaniasis

Abstract

Human infection with Leishmania braziliensis leads to the establishment of cutaneous leishmaniasis (CL), characterized by the appearance of skin lesions that progress from nonulcerated to ulcerated forms. Our goal was to characterize the immunological kinetics associated with this progression, comparing the cellular composition, cytokines and granzyme expression between lesions of patients with early (E-CL) and late stages (L-CL) of CL. Histopathological analysis showed that lesions from L-CL had more exuberant inflammatory infiltrate as compared to E-CL. Although E-CL and L-CL lesions were predominantly mononuclear, lesions from E-CL patients presented higher neutrophil and eosinophil counts than L-CL. While percentages of CD4+ and of CD68+ cells were slightly higher in L-CL, a fivefold increase of CD8+ cells was observed in L-CL, as compared to E-CL. Moreover, CD8+ T-cells from L-CL expressed significantly higher levels of granzyme A than E-CL. Interestingly, granzyme A expression was positively correlated with intensity of the inflammatory infiltrate in L-CL but not E-CL. Lastly, percentages of IFN-c+ and IL-10+ cells were higher in L-CL as compared to E-CL, with CD4+ T-cells and CD68+ monocytes as the main sources of these cytokines, respectively. These results suggest that recruitment of CD8+ granzyme A+ T cells is involved in lesion progression in human CL.