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.
Peterson
K E
KE
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA.
Iwashiro
M
M
Hasenkrug
K J
KJ
Chesebro
B
B
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D005622:Friend murine leukemia virus / Q000276:immunology*; D006183:H-2 Antigens / Q000235:genetics*; D064532:Histocompatibility Antigen H-2D; D007371:Interferon-gamma / Q000096:biosynthesis*; D007942:Leukemia, Experimental / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D017354:Point Mutation; D012192:Retroviridae Infections / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013163:Splenomegaly / Q000276:immunology; D014412:Tumor Virus Infections / Q000276:immunology*
D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D007371:Interferon-gamma