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The Journal of Immunology, Vol 152, Issue 5 2172-2179, Copyright © 1994 by American Association of Immunologists

ARTICLES

Effects of IL-12 on helper T cell-dependent immune responses in vivo

AJ McKnight, GJ Zimmer, I Fogelman, SF Wolf and AK Abbas
Department of Pathology, Brigham & Women's Hospital, Boston, MA 02115.

The differentiation of naive T cells to the Th1 or Th2 subset of effector cells is regulated by the cytokines to which T cells are exposed at the time of antigenic stimulation. Mice immunized with a hapten-protein conjugate and treated systemically with IL-12 show a marked inhibition of IL-4-secreting cells and suppressed production of anti-hapten IgG1 Ab, as well as a marked enhancement of IFN-gamma- producing T cells. Thus, IL-12 is a potent inhibitor of Th2 differentiation and an inducer of Th1 development in vivo. The IFN- gamma-inducing effect of IL-12 is partially blocked by pretreatment of mice with anti-asialo GM1 (anti-NK cell) Ab, but anti-asialo GM1 does not abrogate any of the other systemic actions of IL-12. Furthermore, none of the effects of IL-12 is prevented by treating mice with neutralizing anti-IFN-gamma Abs. These results suggest that the effects of IL-12 may be mediated both via NK cell stimulation and by directly altering the differentiation patterns of T cells. Finally, a neutralizing anti-IL-12 Ab significantly inhibits Th1 responses to Ag, indicating that IL-12 may play an obligatory role in Ag-induced Th1 differentiation in vivo.


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