Müller B, Mitchison A
Deutsches Rheuma Forschungszentrum, Berlin, Germany.
Philos Trans R Soc Lond B Biol Sci. 1997 Sep 29;352(1359):1327-30. doi: 10.1098/rstb.1997.0117.
It has long been known that certain MHC class II genes can dominantly suppress immune responses and so increase susceptibility to parasite infections, but the mechanism has been unclear. Recent work has revealed one way in which this form of suppression may operate, through gating by MHC class II molecules of the back-signal from activated T cells into macrophages. The two known suppressive genes of the mouse are expressed in macrophages more extensively than are other class II genes. This is associated with suppression of IL-4 production resulting, we infer, from overproduction in the macrophages of IL-12, the counter-cytokine to IL-4. The lack of IL-4 may itself be immunosuppressive, even for Th2 responses, and excess IL-12 can overinduce the antiproliferative cytokine IFN-gamma. Although this mechanism requires further substantiation, we believe that it offers a reasonable answer to an old conundrum.
长期以来，人们一直知道某些MHC II类基因可以显性抑制免疫反应，从而增加对寄生虫感染的易感性，但其机制尚不清楚。最近的研究揭示了这种抑制形式可能起作用的一种方式，即通过MHC II类分子对活化T细胞向巨噬细胞发出的反向信号进行门控。小鼠的两个已知抑制基因在巨噬细胞中的表达比其他II类基因更广泛。这与IL-4产生的抑制有关，我们推断这是由于巨噬细胞中IL-12过度产生所致，IL-12是IL-4的反细胞因子。IL-4的缺乏本身可能具有免疫抑制作用，即使对Th2反应也是如此，而过量的IL-12会过度诱导抗增殖细胞因子IFN-γ。尽管这一机制需要进一步证实，但我们认为它为一个古老的难题提供了合理的答案。
