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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-
) in vivo inhibited recovery, which indicated that IFN-
was
a necessary component of the immune response to FV. Furthermore, in
H-2b/b mice, high numbers of IFN-
-producing
cells were detected after FV infection, whereas in
H-2a/b mice, which have a low-recovery
phenotype, only low numbers of IFN-
-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-
-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-
-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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