Article
CD8(+) granzyme B(+)-mediated tissue injury vs. CD4(+)IFNγ(+)-mediated parasite killing in human cutaneous leishmaniasis
Registro en:
SANTOS, C. S. et al. CD8(+) granzyme B(+)-mediated tissue injury vs. CD4(+)IFNγ(+)-mediated parasite killing in human cutaneous leishmaniasis. Journal of Investigative Dermatology, v. 133, p. 1533–1540, 2013.
0022-202X
10.1038/jid.2013.4
Autor
Santos, Claire da Silva
Boaventura, Viviane
Cardoso, Cristina Ribeiro
Tavares, Natalia
Lordelo, Morgana de Jesus
Noronha, Almério
Costa, Jackson
Borges, Valéria de Matos
Oliveira, Camila Indiani de
Van Weyenbergh, Johan
Barral, Aldina Maria Prado
Barral Netto, Manoel
Brodskyn, Claudia Ida
Resumen
Fundação de Amparo a Pesquisa do Estado da Bahia (FAPESB) e/Conselho Nacional de Desenvolvimento
Científico e Tecnológico (CNPq grant number PPSUS # SUS0025/2009) and from Pronex (FAPESB/CNPq grant number 738712006). CdaSS has a fellowship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil. 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.