Generation of nitric oxide by the inducible nitric oxide synthase protectsgamma delta T cells from Mycobacterium tuberculosis-induced apoptosis

gamma delta T cells are early recruited into mycobacterial lesions. Upon mi crobial Ag recognition, gamma delta cells secrete cytokines and chemokines and undergo apoptosis via CD95/CD95 ligand (CD95L) interaction, possibly in fluencing the outcome of infection and the characteristics of the disease. Ln this paper we show that activated phagocytes acquire, upon challenge wit h Mycobacterium tuberculosis, the ability to inhibit M. tuberculosis-induce d gamma delta cell apoptosis, Apoptosis protection was due to NO because it correlated with NO synthase (NOS)-2 induction and activity in scavenger ce lls and was abrogated by NOS inhibitors. Furthermore, the NO donor S-nitros oacetylpenicillamine mimicked the effect of enzyme induction, NO left unaff ected the expression of CD95 and CD95L, suggesting interference with an eve nt ensuing CD95/CD95L interaction. NO was found to interfere with the intra cellular accumulation of ceramide and the activation of caspases, which wer e involved in gamma delta T cells apoptosis after M. tuberculosis recogniti on. We propose that NO generated by infected macrophages determines the lif e span and therefore the function of lymphocytes at the infection site, thu s linking innate and adaptive immunity.