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CD8 cells of patients with diffuse cutaneous leishmaniasis display functional exhaustion: the latter is reversed, in vitro, by TLR2 agonists

By Joselín Hernández-ruiz, Norma Salaiza-suazo, Georgina Carrada, Sofía Escoto, Yvonne Rosenstein, Ro Zentella and Ingeborg Becker

Abstract

Leishmania mexicana (Lm) causes localized (LCL) and diffuse (DCL) cutaneous leishmaniasis. DCL patients have a poor cellular immune response leading to chronicity. It has been proposed that CD8 T lymphocytes (CD8) play a crucial role in infection clearance, although the role of CD8 cytotoxicity in disease control has not been elucidated. Lesions of DCL patients have been shown to harbor low numbers of CD8, as compared to patients with LCL, and leishmanicidal treatment restores CD8 numbers. The marked response of CD8 towards Leishmania parasites led us to analyze possible functional differences between CD8 from patients with LCL and DCL. We compared IFNc production, antigen-specific proliferation, and cytotoxicity of CD8 purified from PBMC against autologous macrophages (MO) infected with Leishmania mexicana (MOi). Additionally, we analyzed tissue biopsies from both groups of patients for evidence of cytotoxicity associated with apoptotic cells in the lesions. We found that CD8 cell of DCL patients exhibited low cytotoxicity, low antigen-specific proliferation and low IFNc production when stimulated with MOi, as compared to LCL patients. Additionally, DCL patients had significantly less TUNEL + cells in their lesions. These characteristics are similar to cellular ‘‘exhaustion’ ’ described i

Year: 2010
OAI identifier: oai:CiteSeerX.psu:10.1.1.352.554
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