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 protective immunity dependent on IFN-gamma and TNF. In this study, we analyzed whether endogenously produced IL-12 was involved in the generation of such protective T cells. We found that the neutralization of IL-12 with the administration of specific mAbs throughout the course of the infection led to the inability of BALB/c mice to control the infection by M. avium strain 2447. On the contrary, the late neutralization of IL-12, with the administration of the mAb starting only at the third week of infection, did not affect the growth of M. avium. The neutralization of IL-12 blocked the induction of protective T cells detected upon adoptive transfer to sublethally irradiated recipient mice. The neutralization of IL-12 in the recipient mice did not affect the protective activity of immune cells, showing that IL-12 is involved mainly 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 immunodeficient (SCID) mice. Finally, animals whose IL-12 was blocked expressed heightened levels of IL-4 and IL-10 message and reduced expression of IFN-gamma as compared with control mice.