An important role for major histocompatibility complex class I-restricted T cells, and a limited role for gamma interferon, in protection of mice against lethal herpes simplex virus infection

Herpes simplex virus (HSV) inhibits major histocompatibility complex (MHC) class I expression in infected cells and does so much more efficiently in h uman cells than in murine cells. Given this difference, if MHC class I-rest ricted T cells do not play an important role in protection of mice from HSV , an important role for these tells in humans would be unlikely. However, t he contribution of MHC class I-restricted T cells to the control of HSV inf ection in mice remains unclear. Further, the mechanisms by which these cell s may act to control infection, particularly in the nervous system, are not well understood, though a role for gamma interferon (IFN-gamma) has been p roposed. To address the roles of MHC class I and of IFN-gamma, C57BL/6 mice deficient in MHC class I expression (beta 2 microglobulin knockout [beta 2 KO] mice), in IFN-gamma expression (IFN-gamma KO mice), or in both (IFN-gam ma KO/beta 2KO mice) were infected with HSV by footpad inoculation. beta 2K O mice were markedly compromised in their ability to control infection, as indicated by increased lethality and higher concentrations of virus in the feet and spinal ganglia. In contrast, IFN-gamma appeared to play at most a limited role in viral clearance. The results suggest that MHC class I-restr icted T cells play an important role in protection of mice against neuroinv asive HSV infection and do so largely by mechanisms other than the producti on of IFN-gamma.