摘要
interleukin 12 (IL-12) is a powerful stimulus for the growth of activated T and natural killer cells,their generation of interferon γ(IFN-γ),and the differentiation of T helper type 1(Th1) effector cells from naive precursors in vitro. Using this characterized model of CD4 cell differentiation, we examined the immunologic effects of IL-12 administered either at the time of infection; when naive T cells are primed,or after 14 days of in fection,by which time CDt subset differentiation has occurred.Given with the inoculationof parasites,IL-12 induced IFN-γand IL-10 and markedly suppressed IL-4. Effects on IL10 and IL-4 are comparable in mice with homozygous disruption of the IFN-γgene (IFNγ%),and suppression of IL-4 was unchanged by administration of neutralizing anti-IL-10antibody.Induction of IFN-γand IL-10 mRNA by IL-12 also occurred in infected SCID mice.Given after day 14 of infection, however, IL-12 not only induced IFN-γand IL-10but also induced IL-4 in normal and IFN-γ% mice. These data demonstrate direct effects of IL-12 independent of IFN-γ IL-10,and IL-4 and demonstrate that the ineffectiveness of IL-12 administered following infection with Leishmania major correlates with resistance of differentiated Th2 cells to the IL-4 suppressing activity of IL-12.
interleukin 12 (IL-12) is a powerful stimulus for the growth of activated T and natural killer cells,their generation of interferon γ(IFN-γ),and the differentiation of T helper type 1(Th1) effector cells from naive precursors in vitro. Using this characterized model of CD4 cell differentiation, we examined the immunologic effects of IL-12 administered either at the time of infection; when naive T cells are primed,or after 14 days of in fection,by which time CDt subset differentiation has occurred.Given with the inoculationof parasites,IL-12 induced IFN-γand IL-10 and markedly suppressed IL-4. Effects on IL10 and IL-4 are comparable in mice with homozygous disruption of the IFN-γgene (IFNγ%),and suppression of IL-4 was unchanged by administration of neutralizing anti-IL-10antibody.Induction of IFN-γand IL-10 mRNA by IL-12 also occurred in infected SCID mice.Given after day 14 of infection, however, IL-12 not only induced IFN-γand IL-10but also induced IL-4 in normal and IFN-γ% mice. These data demonstrate direct effects of IL-12 independent of IFN-γ IL-10,and IL-4 and demonstrate that the ineffectiveness of IL-12 administered following infection with Leishmania major correlates with resistance of differentiated Th2 cells to the IL-4 suppressing activity of IL-12.
