CD137 differentially regulates innate and adaptive immunity against Mycobacterium tuberculosis.

FERNANDEZ DO PORTO DA; JURADO J.O; PASQUINELLI V; ALVAREZ IB; ASPERA RH; MUSELLA RM; GARCIA VE

IMMUNOLOGY AND CELL BIOLOGY

NATURE PUBLISHING GROUP

Año: 2012 vol. 90 p. 449 - 456

0818-9641

Protective immunity against Mycobacterium tuberculosis is primarily mediated by the interaction of antigen-specific T cells and APC, which often depends on the interplay of cytokines produced by these cells. Costimulatory signals represent a complex network of receptor-ligand interactions that qualitatively and quantitatively influence immune responses. Thus, here we investigated the function of CD137 and CD137L, molecules known to play a central role in immune regulation, during human tuberculosis. We demonstrated that specific antigen-stimulation increased both CD137 and CD137L expression on monocytes and NK cells from tuberculosis patients and healthy donors, but only up-regulated CD137 on T lymphocytes. Blockage of the CD137 pathway enhanced the levels of IFN-gamma and TNF-alpha produced by monocytes and NK against M. tuberculosis. In contrast, CD137 blockage significantly decreased the specific degranulation of CD8+ T cells and the percentage of specific IFN-gamma and TNF-alpha producing lymphocytes against the pathogen. Furthermore, inhibition of the CD137 pathway markedly increased T cell apoptosis. Taken together, our results demonstrate that CD137:CD137L interactions regulate the innate and adaptive immune response of the host against M. tuberculosis.