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

Abstract

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 responder H-2 b allele at major histocompatibility complex (MHC) class II loci, a single H-2D b MHC class I allele was sufficient for the development of a CD4 + Th1 response to FV. This effect of H-2D b on 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 nonresponder H-2 a/a mice induced FV-specific responses of H-2D d -restricted CD8 + cytotoxic T lymphocytes (CTL). Adoptive transfer of vaccine-primed CD8 + T cells to naive H-2 a/a mice 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.