BACILLE CALMETTE-GUERIN VACCINATION ENHANCES HUMAN GAMMA-DELTA T-CELLRESPONSIVENESS TO MYCOBACTERIA SUGGESTIVE OF A MEMORY-LIKE PHENOTYPE

Bacille Calmette-Guerin (BCG) immunity can be studied as one experimen tal model for mycobacterial protective immunity. We have used flow cyt ometry to investigate human T cell subsets induced by BCG vaccination. PBMC harvested from BCG-vaccinated individuals and controls were stim ulated with mycobacterial Ags, and the T cell subsets present after 7 days of in vitro expansion were characterized, The most dramatic expan sions induced by mycobacterial Ags were detected in gamma delta T cell s. The gamma delta T cell expansions measured after in vitro stimulati on with mycobacterial Ags were significantly greater in BCG responders compared with nonsensitized controls, indicating that BCG vaccination induced gamma delta T cell activation associated with enhanced second ary responses. The majority of gamma delta T cells induced by BCG vacc ination were gamma(9)(+)delta(2)(+) T cells reactive with isoprenyl py rophosphates. Coculture with CD4(+) T cells induced optimal gamma delt a T cell expansion, although IL-2 alone could provide this helper func tion in the absence of CD4(+) T cells. gamma delta T cells were found to provide helper functions for mycobacterial specific CD4+ and CD8(+) T cells as well, demonstrating reciprocal stimulatory interactions be tween gamma delta T cells and other T cell subsets. Finally, prominent mycobacterial specific gamma delta T cell expansions were detected in a subset of unvaccinated controls with evidence for prior sensitizati on to mycobacterial lysates (elevated mycobacterial specific lymphopro liferative responses). These latter findings are consistent with the h ypothesis that exposure to atypical mycobacteria or related environmen tal Ags may induce gamma delta T cells cross-reactive with Ags present in the Mycobacterium tuberculosis complex, Our results suggest that g amma delta T cells may be capable of developing a memory immune-like p henotype, and therefore might be important targets for new vaccines.