The primary response of human γ/δ+ T cells to Mycobacterium tuberculosis is restricted to Vγ9-bearing cells

Abstract

We have previously reported that peripheral blood γ/δ+ T cells proliferate in high frequency (1 in 2-20) in response to heat-killed Mycobacterium tuberculosis (M.tb.). In the present study, the T cell receptor phenotype of mycobacteria-responsive human γ/δ+ T cells was analyzed in primary cultures with a set of monoclonal antibodies (mAbs) directed against Vγ9, Vδ1, and Vδ2. When unseparated T cells were stimulated with M.tb., all proliferating γ/δ+ T cells expressed Vγ9 (and Vδ2) after culture. Selective depletion of Vγ9-bearing cells before culture completely abolished the proliferative response of all γ/δ+ T cells (but did not inhibit reactivity of α/β+ T cells). In addition, when CD4-CD8- thymocytes were stimulated with M.tb., there was again selective outgrowth of Vγ9+ cells. In this case, the starting responder population contained few (0.5-1.8%) Vγ9+ and many (11.5-31.5%) Vδ1+ cells that did not coexpress Vγ9. These Vδ1+ cells were not activated by M.tb. but could be readily stimulated by anti-Vδ1 mAb A13. Finally, a Vγ9-specific mAb selectively suppressed the proliferative response of γ/δ+ T cells to M.tb. Taken together, our results demonstrate that, within γ/δ+ T cells, reactivity towards M.tb. is an exclusive property of Vγ9+/Vδ2+-bearing cells.