McKnight A J, Zimmer G J, Fogelman I, Wolf S F, Abbas A K
Department of Pathology, Brigham & Women's Hospital, Boston, MA 02115.
J Immunol. 1994 Mar 1;152(5):2172-9.
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.
初始T细胞向效应细胞的Th1或Th2亚群分化受抗原刺激时T细胞所接触的细胞因子调控。用半抗原-蛋白质偶联物免疫并经IL-12全身处理的小鼠，分泌IL-4的细胞显著受到抑制，抗半抗原IgG1抗体的产生受到抑制，同时产生IFN-γ的T细胞显著增加。因此，IL-12在体内是Th2分化的有效抑制剂和Th1发育的诱导剂。用抗唾液酸GM1（抗NK细胞）抗体预处理小鼠可部分阻断IL-12的IFN-γ诱导效应，但抗唾液酸GM1并不消除IL-12的任何其他全身作用。此外，用中和性抗IFN-γ抗体处理小鼠并不能阻止IL-12的任何效应。这些结果表明，IL-12的效应可能通过NK细胞刺激以及直接改变T细胞的分化模式来介导。最后，一种中和性抗IL-12抗体显著抑制Th1对抗原的反应，表明IL-12在体内抗原诱导的Th1分化中可能起关键作用。
