During murine neurotropic coronavirus infection CD8 T cells are critical anti-viral effectors, while CD4 T cells play a prominent role in the disease and demyelination associated with the infection. The failure of CD8 T cells to control infection in the absence of CD4 T cells implied that CD8 T cells require CD4 T help in this encephalomyelitis model. To explore whether CD4 T cell help was imprinted early during the priming and CD8 T cell expansion phase, CD4 T cells were not depleted until days 4 and 6 post-infection. Disease onset and progression was comparable between depleted and control groups, with CD4 depleted mice displaying slightly less severe clinical symptoms. Peripheral expansion of virus-specific CD8 T cells was also comparable to controls and recruitment of virus-specific CD8 T cells into the CNS was only slightly diminished. Nevertheless, control of infectious virus was impaired following CD4 T cell depletion and mice succumbed to infection. Failure to control virus correlated with reduced IFN-gamma in the CNS, as well as lower granzyme B and perforin mRNA levels in CD8 T cells. Impaired CD8 T cell activity coincided with the absence of CD4 dependent IL-21 expression in the CNS. These results indicate that the presence of CD4 T cells during priming does not rescue impaired CD8 T cell function within the CNS. The data rather suggest that CD4 T cell play a critical role in promoting CD8 T cell function and accumulation at the site of infection.
- Copyright © 2011 by The American Association of Immunologists, Inc.