ENDOGENOUSLY PRODUCED IL-12 IS REQUIRED FOR THE INDUCTION OF PROTECTIVE T-CELLS DURING MYCOBACTERIUM-AVIUM INFECTIONS IN MICE

Immunity to Mycobacterium avium depends on the induction of protective CD4(+) T cells. In mice, M. avium induces a Th1 response leading to p rotective immunity dependent on IFN-gamma and TNF. In this study, we a nalyzed whether endogenously produced IL-12 was involved in the genera tion of such protective T cells. We found that the neutralization of I L-12 with the administration of specific mAbs throughout the course of the infection led to the inability of BALB/c mice to control the infe ction by M. avium strain 2447. On the contrary, the late neutralizatio n of IL-12, with the administration of the mAb starting only at the th ird week of infection, did not affect the growth of M. avium. The neut ralization of IL-12 blocked the induction of protective T cells detect ed upon adoptive transfer to sublethally irradiated recipient mice. Th e neutralization of IL-12 in the recipient mice did not affect the pro tective activity of immune cells, showing that IL-12 is involved mainl y in the induction, and not the expression, of acquired cell-mediated immunity. IL-12 was also shown to be required for a T cell-independent pathway of resistance present in T cell-deficient severe combined imm unodeficient (SCID) mice. Finally, animals whose IL-12 was blocked exp ressed heightened levels of IL-4 and IL-10 message and reduced express ion of IFN-gamma as compared with control mice.