CD8+ T cells in situ in different clinical forms of human cutaneous leishmaniasis

Abstract

Introduction Leishmania braziliensis infection induces a large spectrum of lesions that clinically manifest as nodules or papules that progress to ulcers. Although it is already known that T helper cells predominate in the lesions, cytotoxic T cells have also been reported to be present, and their role in leishmaniasis immunopathogenesis is not well known. This study investigated the amounts of CD8+ and granzyme B+ cells in different clinical forms of human cutaneous leishmaniasis (CL). Methods Forty tissue fragments from early (E-CL) and late CL (L-CL) lesions and from disseminated leishmaniasis (DL) - papules and ulcers - were characterized. The inflamed area per fragment was calculated, and the CD8 and granzyme B expression levels in the infiltrates were quantified by counting positive cells in 15 fields. The localization of CD8 and granzyme B was graded subjectively. Results Inflammation was higher in L-CL and DL ulcers. CD8 expression was increased in late ulcerated lesions compared to recent lesions. The increase in CD8+ cells also correlated with the duration of the lesion. Papules had a higher frequency of granzyme B+ cells than E-CL lesions, although the frequency was similar to those for late and DL ulcers. CD8+ cells were mostly found in the papillary dermis. Conclusions CD8+ T and granzyme B+ cells are present in the inflammatory infiltrates of CL and DL and may participate in the immunopathogenesis of Leishmania infection.

Characterization of the Histopathologic Features in Patients in the Early and Late Phases of Cutaneous Leishmaniasis

“…Although there was no association between CD8 + T cells expressing granzyme and the area of inflammation in E-CL, there was a correlation between the frequency of CD8 + T cells expressing granzyme and the intensity of the inflammatory reaction in L-CL 26. Moreover, although CD8 + T cells kill L. braziliensis –infected cells, they have an impairment in parasite killing 4,5,23. The inflammatory reaction in both E-CL and L-CL is composed of CD68 + , CD4 + and CD8 + T cells as well as B cells.…”

“…Although the T-cell response is important to prevent parasite dissemination, an exaggerated inflammatory response is associated with pathology 22,23. We have previously shown a direct correlation between the frequency of CD4 + T cells expressing IFN and TNF, and CD4 + T cells expressing lymphocyte activation markers with the lesion size 22,24.…”

American cutaneous leishmaniasis: In situ immune response of patients with recent and late lesions

“…Consequently, both groups of patients expressed similar concentrations of CD68 cells in order to kill amastigotes in infected cells. However, such cytotoxicity is directly correlated with expressed granzyme causing ulcer development …”

“…However, such cytotoxicity is directly correlated with expressed granzyme causing ulcer development. 20,41,42 The comparison of cytokine expression per group (Figure 4) showed that IL-10 was significantly higher than IL-17 and IFNγ. These data suggest an immunological balance between inflammatory-antiinflammatory agents, and such balance was similar for two groups of patients.…”

In VitroImmunomodulatory Activity of a Transition-State Analog Inhibitor of Human Purine Nucleoside Phosphorylase in Cutaneous Leishmaniasis

“…High lymphocyte proliferation is also characteristic of CL, and we showed that DI4G decreased lymphocyte proliferation predominantly in CD8 + T cells rather than in CD4 + T cells. The role of inflammatory and cytotoxic CD8 + T cells in the pathology of CL has been well documented [ 7 , 30 , 36 , 37 ]. More recently, evidence has been brought that CD8 + T cells play a key role not only in the inflammatory response and ulcer development but also in the appearance of metastatic lesions in CL [ 38 ].…”