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 five-fold 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 granzymeA than E-CL. Interestingly, granzymeA expression was positively correlated with intensity of the inflammatory infiltrate in L-CL but not E-CL. Lastly, percentages of IFN-γ + 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+granzymeA+ T-cells is involved in lesion progression in human CL.

Impaired T‐cell‐dependent protection against Leishmania major infection in HIV‐positive patients is associated with worsened disease outcome

“…This is in line with the association of IFN-cproducing CD4 + T cells and the healing of lesions observed in murine experimental CL (4). In contrast, the role of CD8 + cells for healing in human CL is controversially discussed ranging from beneficial to no effect (7), or even enhancement of lesion ulceration (8). Our present study corroborates earlier reports that suggest that antigen-specific CD8 + T cells alone are not sufficient for the clearance of CL.…”

Chronicity of Dermal Leishmaniasis Caused by Leishmania panamensis Is Associated with Parasite-Mediated Induction of Chemokine Gene Expression

“…Chronic dermal leishmaniasis has been associated with immunological hyperreactivity (5,6), overproduction of pro-and anti-inflammatory cytokines (21), and scarce but persistent parasites at the lesion site (4). Upregulation of inflammatory functions is accompanied by increased cellular infiltration of lesions, perpetuating the immunopathology (23,24). We have previously shown that macrophage permissiveness for survival and replication of intracellular Leishmania correlates with the clinical outcome of infection; macrophages from patients with chronic CL were more permissive to infection than were cells from individuals with asymptomatic disease (25).…”

Inhibitory Receptor Expression on CD8+ T Cells Is Linked to Functional Responses against Trypanosoma cruzi Antigens in Chronic Chagasic Patients

“…In this study, cytotoxic activity was higher in CD8 + T cells at the late stage of differentiation in patients with more severe forms of cardiac disease, whereas the production of IL-2 in CD8 + T cells was lower. Studies have shown that the severity of the disease, that is, tissue damage, resulting from Leishmania braziliensis infection is directly correlated with more granzymeproducing CD8 + T cells (76) and that CD8 + T cell-mediated cytotoxicity promotes lesions in cutaneous leishmaniasis (77). In addition, CD8 + T cells producing perforin might play a detrimental role in experimental T. cruzi infection in mice, leading to heart injury (78).…”