Induction of apoptosis in bacillus Calmette-Guerin-activated T cells by transforming growth factor-beta

In view of the critical role played by bacillus Calmette-Guerin (BCG) in th e development and functional activation of protective T cells against tuber culosis, it has become important to understand the mechanisms by which cyto kines regulate BCG-mediated immune responses. There is evidence that cytoki ne-mediated suppression of T cell function by mechanisms, including apoptos is, may reduce host resistance in tuberculosis. However, it is unclear whet her cytokine-mediated suppression of antigen-responsive T cells through apo ptotic mechanisms may be operating during human cellular activation induced by BCG. Here we present evidence, for the first time, that treatment of BC G-activated T cells with transforming growth factor-beta (TGF-beta) induces cellular apoptosis. These results were further supported by the fact that treatment of cells with a blocking mAb directed to TGrF-beta significantly inhibited the percentage of apoptosis induced by TGF-beta. Interestingly, T GF-beta-mediated death of BCG-activated T cells in cultures containing inte rleukin (IL)-12 was observed. Moreover, our results demonstrated the induct ion of apoptosis by TGF-beta in BCG-activated T cells cultured in the prese nce of exogenous IL-12. In addition, our data indicated that TGF-beta signi ficantly inhibited both BCG-induced cell growth determined by thymidine upt ake and BCG-induced IFN-gamma secretion. Finally, TGF-beta-induced apoptosi s in BCG-activated T cells correlated inversely with BCG-induced IFN-gamma secretion. Taken together, these findings indicate that TGF-beta induces ap optosis in human T cells activated with BCC: and at the same time suggest t hat loss of BCG-reactive T cells through apoptotic mechanisms could contrib ute to an increased susceptibility to Mycobacterium tuberculosis infection, (C) 2000 Academic Press.