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Journal of Virology, June 2000, p. 5363-5367, Vol. 74, No. 11
0022-538X/00/$04.00+0

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

Karin E. Peterson, Michihiro Iwashiro, Kim J. Hasenkrug, and Bruce Chesebro*

Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840

Received 18 January 2000/Accepted 29 February 2000

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-2b/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-2b/b mice, high numbers of IFN-gamma -producing cells were detected after FV infection, whereas in H-2a/b mice, which have a low-recovery phenotype, only low numbers of IFN-gamma -producing cells were detected. Similarly, H-2bm14/b mice, which cannot recover from FV infection due to a point mutation in one allele of the H-2Db 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.

* Corresponding author. Mailing address: Rocky Mountain Laboratories, 903 S. 4th St., Hamilton, MT 59840. Phone: (406) 363-9354. Fax: (406) 363-9286. E-mail: bchesebro{at}nih.gov.

Journal of Virology, June 2000, p. 5363-5367, Vol. 74, No. 11
0022-538X/00/$04.00+0


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