Novel Role of CD8+T Cells and Major Histocompatibility Complex Class I Genes in the Generation of Protective CD4+Th1 Responses during Retrovirus Infection in Mice

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Abstract
CD4+Th1 responses to virus infections are often necessary for the development and maintenance of virus-specific CD8+T-cell responses. However, in the present study with Friend murine retrovirus (FV), the reverse was also found to be true. In the absence of a responderH-2ballele at major histocompatibility complex (MHC) class II loci, a singleH-2DbMHC class I allele was sufficient for the development of a CD4+Th1 response to FV. This effect ofH-2Dbon CD4+T-cell responses was dependent on CD8+T cells, as demonstrated by depletion studies. A direct effect of CD8+T-cell help in the development of CD4+Th1 responses to FV was also shown in vaccine studies. Vaccination of nonresponderH-2a/amice induced FV-specific responses ofH-2Dd-restricted CD8+cytotoxic T lymphocytes (CTL). Adoptive transfer of vaccine-primed CD8+T cells to naiveH-2a/amice prior to infection resulted in the generation of FV-specific CD4+Th1 responses. This novel helper effect of CD8+T cells could be an important mechanism in the development of CD4+Th1 responses following vaccinations that induce CD8+CTL responses. The ability of MHC class I genes to facilitate CD4+Th1 development could also be considerable evolutionary advantage by allowing a wider variety of MHC genotypes to generate protective immune responses against intracellular pathogens.