PRIMARY ACTIVATION OF V-GAMMA-9-EXPRESSING GAMMA-DELTA T-CELLS BY MYCOBACTERIUM-TUBERCULOSIS - REQUIREMENT FOR TH1-TYPE CD4 T-CELL HELP ANDINHIBITION BY IL-10

Purified peripheral blood gamma delta T cells proliferated vigorously in response to killed Mycobacterium tuberculosis (M. tb.) in the prese nce of PBMC but not in the presence of T cell-depleted (E(-)) feeder c ells. Addition of graded numbers of autologous CD4 T cells to E(-) fee der cells reconstituted in a dose-dependent fashion the response of V gamma 9-expressing gamma delta T cells to M. tb. IL-2 was identified a s the major CD4 T cell-derived helper factor required for gamma delta T cell proliferation after stimulation with M. tb. In addition, neutra lizing anti-IFN-gamma but not anti-IFN-alpha Ab inhibited the responsi veness of V gamma 9 T cells, suggesting that endogenously produced IFN -gamma was involved in the activation of gamma delta T cells by M. tb. Although gamma delta T cells could not proliferate on their own in th e absence of CD4 T cells (or exogenous IL-2), the appearance of IL-2 r eceptors (CD25) was triggered in the absence of CD4 T cells. Furthermo re, IL-10 strongly inhibited the activation of V gamma 9 T cells among unfractionated PBMC responder cells. Similarly, the responsiveness of purified gamma delta T cells to M. tb. occurring in the presence of C D4 T cells was strongly inhibited by IL-10, whereas the activation occ urring in the presence of exogenous IL-2 was not impaired. These resul ts show that interactions with Th1-type CD4 T cells are required for e fficient activation of peripheral blood gamma delta T cells by M. tb. In addition, our results have practical implications for creating expe rimental conditions aimed at identifying V gamma 9-selective (myco)bac erial ligands.