Naive human T cells develop into Th1 effectors after stimulation with Mycobacterium tuberculosis-infected macrophages or recombinant Ag85 proteins

Most studies of human T-cell responses in tuberculosis have focused on pers ons with either active disease or latent infection. Although this work has been critical in defining T-cell correlates of successful versus failed hos t containment, little is known about the development of Mycobacterium-speci fic T-cell responses in uninfected persons. To explore this issue, naive T cells from uninfected donors were sensitized in vitro with avirulent Mycoba cterium tuberculosis-infected autologous macrophages. T cell lines primed i n this manner proliferated and produced cytokines after challenge with myco bacterial antigens. Of 11 such lines, 8 were high Th1 responders, 2 were lo w Th1 responders, and 1 was a Th2 responder. Furthermore, similar patterns and magnitudes of proliferative and cytokine responses were seen when Mycob acterium infection-primed lines were challenged with recombinant antigen 85 (Ag85) proteins. The addition of interleukin 12 (IL-12) during the initial sensitization increased the magnitude of Th1 responses; however, antibody to IL-12 did not eliminate Th1 responses, suggesting that additional factor s contributed to the differentiation of these cells. Finally, in the presen ce of IL-12, recombinant Ag85B was able to prime naive T cells for Th1 resp onses upon challenge with Mycobacterium-infected macrophages or Ag85B. Ther efore, under the appropriate conditions, priming with whole bacteria or a s ubunit antigen can stimulate Mycobacterium-specific Th1 effector cell devel opment. Further definition of the antigens and conditions required to drive naive human T cells to differentiate into Th1 effecters should facilitate the development of an improved tuberculosis vaccine.