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

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-gamma) in vivo inhibited recovery, which indicated that IFN-gamma was a necessary component of the immune response to FV. Furthermore, in H-2(b/b) mice, high numbers of IFN-gamma-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-gamma-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-gamma-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-gamma-producing CD4(+) and CD8(+) T cells helps explain the major impact of the H-2D gene on recovery from FV disease.