The importance of the back-signal from T cells into antigen-presenting cells in determining susceptibility to parasites

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.