Induction of Apoptosis in Bacillus Calmette–Guérin-Activated T Cells by Transforming Growth Factor-β

• Published in: Cellular immunology 2000-06, Vol.202 (2), p.103-112
• Main Authors: Méndez-Samperio, Patricia, Hernández-Garay, Marisol, Garcı́a-Martı́nez, Elizabeth
• Format: Article
• Language: English
• Subjects: Apoptosis - immunology; Cells, Cultured; Humans; Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - immunology; Lymphocyte Activation; Mycobacterium bovis - immunology; Mycobacterium tuberculosis; T-Lymphocytes - cytology; T-Lymphocytes - immunology; Transforming Growth Factor beta - immunology; Transforming Growth Factor beta - pharmacology; transforming growth factor-^b
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1006/cimm.2000.1662

In view of the critical role played by bacillus Calmette–Guérin (BCG) in the development and functional activation of protective T cells against tuberculosis, it has become important to understand the mechanisms by which cytokines regulate BCG-mediated immune responses. There is evidence that cytokine-mediated suppression of T cell function by mechanisms, including apoptosis, may reduce host resistance in tuberculosis. However, it is unclear whether cytokine-mediated suppression of antigen-responsive T cells through apoptotic mechanisms may be operating during human cellular activation induced by BCG. Here we present evidence, for the first time, that treatment of BCG-activated T cells with transforming growth factor-β (TGF-β) induces cellular apoptosis. These results were further supported by the fact that treatment of cells with a blocking mAb directed to TGF-β significantly inhibited the percentage of apoptosis induced by TGF-β. Interestingly, TGF-β-mediated death of BCG-activated T cells in cultures containing interleukin (IL)-12 was observed. Moreover, our results demonstrated the induction of apoptosis by TGF-β in BCG-activated T cells cultured in the presence of exogenous IL-12. In addition, our data indicated that TGF-β significantly inhibited both BCG-induced cell growth determined by thymidine uptake and BCG-induced IFN-γ secretion. Finally, TGF-β-induced apoptosis in BCG-activated T cells correlated inversely with BCG-induced IFN-γ secretion. Taken together, these findings indicate that TGF-β induces apoptosis in human T cells activated with BCG and at the same time suggest that loss of BCG-reactive T cells through apoptotic mechanisms could contribute to an increased susceptibility to Mycobacterium tuberculosis infection.