We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
CD8<sup>+</sup> Granzyme B<sup>+</sup>-Mediated Tissue Injury vs. CD4<sup>+</sup>IFNγ<sup>+</sup>-Mediated Parasite Killing in Human Cutaneous Leishmaniasis.
- Authors
Santos, Claire da Silva; Boaventura, Viviane; Ribeiro Cardoso, Cristina; Tavares, Natalia; Lordelo, Morgana J; Noronha, Almério; Costa, Jackson; Borges, Valéria M.; de Oliveira, Camila I; Van Weyenbergh, Johan; Barral, Aldina; Barral-Netto, Manoel; Brodskyn, Cláudia Ida
- 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.
- Subjects
T cells; LYMPHOCYTES; CUTANEOUS leishmaniasis; PROTOZOAN diseases; ANTIGEN presenting cells
- Publication
Journal of Investigative Dermatology, 2013, Vol 133, Issue 6, p1533
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1038/jid.2013.4