Df. Hoft et al., BACILLE CALMETTE-GUERIN VACCINATION ENHANCES HUMAN GAMMA-DELTA T-CELLRESPONSIVENESS TO MYCOBACTERIA SUGGESTIVE OF A MEMORY-LIKE PHENOTYPE, The Journal of immunology (1950), 161(2), 1998, pp. 1045-1054
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.