The recognition of phosphorylated nonpeptidic microbial metabolites by Vy9V62 T cells does not appear to require the presence of MHC molecules or antigen processing, pennitting rapid responses against microbial pathogens. These may constitute an imnportant area of natural anti-infectious immunity. To provide evidence of their involvement in immune reactivities against mycobacteria, we measured the responsiveness of peripheral blood Vy9V62 T cells in children with primary Mycobacterium

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... is (MTB) infections. Materials and Methods: Peripheral blood mononudear cells from 22 children with MTB infections and 16 positivity of tuberculin (PPD)-negative healthy children were exposed to nonpeptidic antigens in vitro and the reactivity of the Vy9V62 T cell subset with these antigens was determined using proliferation and cytokine assays. Also, responses of yS T cells from rhesus monkeys stimulated with phosphoantigens in vivo were measured. Results: The Vy9Va2 T cell responses were highly increased in infected children in comparison with agematched controls. This augmented Vy9V62 T cell reactivity subsided after successful antibiotic chemotherapy, suggesting that persistent exposure to mycobacterial antigens is required for the maintenance of 'y6 T cell activation in vivo. The in vivo reactivity of Vy9VS2 T cells to phosphoantigens was also analyzed in a rhesus monkey model system. Intravenous injections of phosphoantigens induced an activated state of simian Vy9V82 T cells which decreased after 2 months, i.e., with a time course similar to that seen in MTB-infected children. Conclusions: The increased reactivity of Vy9V62 T cells to phosphoantigens appears to be dependent on constant antigenic exposure. Consequently, the assessment of Vy9VS2 responses may be useful for monitoring the efficacy of antimycobacterial therapies.