title: CD8(+) granzyme B(+)-mediated tissue injury vs. CD4(+)IFNγ(+)-mediated parasite killing in human cutaneous leishmaniasis.
abstract: A protective or deleterious role of CD8(+)T cells in human cutaneous leishmaniasis (CL) has been debated. The present report explores the participation of CD8(+)T cells in disease pathogenesis as well as in parasite killing. CD8(+)T cells accumulated in CL lesions as suggested by a higher frequency of CD8(+)CD45RO(+)T cells and CD8(+)CLA(+)T cells compared with peripheral blood mononuclear cells. Upon Leishmania braziliensis restimulation, most of the CD8(+)T cells from the lesion expressed cytolytic markers, CD107a and granzyme B. Granzyme B expression in CL lesions positively correlated with lesion size and percentage of TUNEL-positive cells. We also observed a significantly higher percentage of TUNEL-positive cells and granzyme B expression in the biopsies of patients showing a more intense necrotic process. Furthermore, coculture of infected macrophages and CD8(+)T lymphocytes resulted in the release of granzyme B, and the use of granzyme B inhibitor, as well as z-VAD, Fas:Fc, or anti-IFN-γ, had no effect upon parasite killing. However, coculture of infected macrophages with CD4(+)T cells strongly increased parasite killing, which was completely reversed by anti-IFN-γ. Our results reveal a dichotomy in human CL: CD8(+) granzyme B(+)T cells mediate tissue injury, whereas CD4(+)IFN-γ(+)T cells mediate parasite killing.
authors: Universidade Federal da Bahia, Salvador, Brazil.
authors: Claire da Silva
authors: Cda S
authors: Santos
authors: Viviane
authors: V
authors: Boaventura
authors: Cristina
authors: C
authors: Ribeiro Cardoso
authors: Natalia
authors: N
authors: Tavares
authors: Morgana J
authors: MJ
authors: Lordelo
authors: Almério
authors: A
authors: Noronha
authors: Jackson
authors: J
authors: Costa
authors: Valéria M
authors: VM
authors: Borges
authors: Camila I
authors: CI
authors: de Oliveira
authors: Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Belgium
authors: Johan
authors: J
authors: Van Weyenbergh
authors: Aldina
authors: A
authors: Barral
authors: Manoel
authors: M
authors: Barral-Netto
authors: Cláudia Ida
authors: CI
authors: Brodskyn
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000469:parasitology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000469:parasitology; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D053804:Granzymes / Q000276:immunology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D007371:Interferon-gamma / Q000276:immunology*; D007892:Leishmania braziliensis / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology / Q000469:parasitology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007371:Interferon-gamma; C509213:GZMB protein, human; D053804:Granzymes