Major Histocompatibility Complex Class I Gene Controls the Generation of Gamma Interferon-Producing CD4 + and CD8 + T Cells Important for Recovery from Friend Retrovirus-Induced Leukemia

Abstract

ABSTRACT Recovery from leukemia induced by Friend virus complex (FV) requires strong CD4 + helper, CD8 + cytotoxic T-lymphocyte, and B-cell responses. The development of these immune responses is dependent on the major histocompatibility complex (MHC) ( H-2 ) genotype of the mouse. In H-2 b/b mice, which spontaneously recover from FV-induced erythroleukemia, neutralization of gamma interferon (IFN-γ) in vivo inhibited recovery, which indicated that IFN-γ was a necessary component of the immune response to FV. Furthermore, in H-2 b/b mice, high numbers of IFN-γ-producing cells were detected after FV infection, whereas in H-2 a/b mice, which have a low-recovery phenotype, only low numbers of IFN-γ-producing cells were detected. Similarly, H-2 bm14/b mice, which cannot recover from FV infection due to a point mutation in one allele of the H-2D b gene, also had low numbers of IFN-γ-producing T cells. Surprisingly, this effect was observed for both CD8 + and CD4 + T cells. These findings reveal a novel influence of MHC class I genes on CD4 + T-cell responses to viral infection. Furthermore, the influence of MHC class I genotype on the generation of both IFN-γ-producing CD4 + and CD8 + T cells helps explain the major impact of the H-2D gene on recovery from FV disease.