THE PRIMARY RESPONSE OF HUMAN GAMMA DELTA+ T-CELLS TO MYCOBACTERIUM-TUBERCULOSIS IS RESTRICTED TO V-GAMMA-9-BEARING CELLS

We have previously reported that peripheral blood-gamma/delta+ 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-gamma/delta+ T cells was analyzed in primary cultures with a set of monoclonal antibodies (mAbs) directed against V-gamma-9, V-delta-1, and V-delta-2. When unseparated T cells were stimulated with M.tb., all proliferating-gamma/delta+ T cells expressed V-gamma-9 (and V-delta-2) after culture. Selective depletion of V-gamma-9-bearing cells before culture completely abolished the proliferative response of all gamma/delta+ T cells (but did not inhibit reactivity of alpha/beta+ T cells). In addition, when CD4-CD8- thymocytes were stimulated with M.tb., there was again selective outgrowth of V-gamma-9+ cells. In this case, the starting responder population contained few (0.5-1.8%) V-gamma-9+ and many (11.5-31.5%) V-delta-1+ cells that did not coexpress V-gamma-9. These V-delta-1+ cells were not activated by M.tb. but could be readily stimulated by anti-V-delta-1 mAb A13. Finally, a V-gamma-9-specific mAb selectively suppressed the proliferative response of gamma/delta+ T cells to M.tb. Taken together, our results demonstrate that, within gamma/delta+ T cells, reactivity towards M.tb. is an exclusive property of V-gamma-9+/V-delta-2+-bearing cells.