Multidrug-resistant M.tuberculosis strain M induces low expression of CD69 and IL-2 in circulating CD8+ T cells

GEFFNER, LAURA; ; BASILE, JUAN; ; SABIO Y GARCÍA, CARMEN; ; BARRERA, LUCÍA;; RITACCO, VIVIANA; ; SASIAIN, M. DEL CARMEN; ; DE LA BARRERA, SILVIA.

Congreso; Primer congreso Franco-Argentino de Inmunología; 2010

Antigen-specific cytotoxic T cell (CTL) activity has been associated to the lysis of infected macrophages and Mycobacterium tuberculosis (Mtb). Previously, we have demonstrated that the multidrug resistant tuberculosis (MDR-TB) outbreak strain M induces weak CTL response associated with low expression of lytic molecules, when compared with its related strain 410 (non prosperous). The aim of this work was to evaluate the mechanisms employed by M to hamper CTL response. Methods: Peripheral blood mononuclear cells (PBMC) isolated from buffy coats were cultured for 18h or 5d with M or 410 strains. Then we evaluated the surface expression of CD69 and CD25 (early and late activation), CD107 (degranulation marker) and the intracytoplasmatic expression of IL-2 in CD8+CD3+T cells by flow cytometry. Results: M induced a lower CD69 expression than 410 (p<0.05) in 18 h cultures, while CD25 expression in 5d cultures was not significantly different between those strains. Both strains induced a similar CD69 peak of expression (66h), thus M strain was not delaying T cell activation. PBMC preincubated with Mtb strains were activated with anti-CD3 with or not anti-CD28 and no inhibition was detected in terms of CD69 expression suggesting that low CD69 expression was not due to an inhibition of TCR activation by strain M. However, M-induced a reduced IL-2 expression in CD8+CD3+T (p<0.05), cytokine that is regulated upon CD69 signaling and controls upregulation of lytic molecules. Besides, blockade of CD69 with specific monoclonal antibody along 5d cultures inhibited CD107 expression in 410-stimulated CD8+ T cells resulting in a CD107 expression similar to that observed in M-stimulated cells. Conclusions: Our preliminary results indicate that low CTL response induced by M could be due to a low CD69 expression in M-stimulated CD8+ T cells that could impact on lytic degranulation and IL-2 production, cytokine that is known to modulate lytic molecule expression.