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Journal of Virology, November 1998, p. 9400-9403, Vol. 72, No. 11
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Requirement for CD4+ T Cells in the Friend Murine Retrovirus Neutralizing Antibody Response: Evidence for Functional T Cells in Genetic Low-Recovery Mice

Heidi J. Super, Diane Brooks, Kim 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 8 April 1998/Accepted 1 August 1998

Recovery from infection with the Friend murine leukemia retrovirus complex (FV) requires T-helper cells and cytotoxic T cells as well as neutralizing antibodies. Several host genes, including genes of the major histocompatibility complex (H-2) and an H-2-unlinked gene, Rfv-3, influence these FV-specific immune responses. (B10.A × A/Wy)F1 mice, which have the H-2a/a Rfv-3r/s genotype, fail to mount a detectable FV-specific T-cell proliferative response but nevertheless produce FV-specific neutralizing immunoglobulin M (IgM) antibodies and can eliminate FV viremia. Thus, this IgM response, primarily influenced by the Rfv-3 gene, may be T-cell independent. To test this idea, mice were depleted of either CD4+ or CD8+ T-cell populations in vivo and were monitored for the effect on the neutralizing antibody response following FV infection. Surprisingly, mice in which CD4+ cells were depleted showed undetectable FV-neutralizing antibody responses and high viremia levels compared to nondepleted or CD8-depleted animals. In addition to knocking out the FV antibody response, CD4+ T-cell depletion reduced survival time significantly, further indicating the importance of CD4+ T cells. These studies revealed the first evidence for a functional T-cell response following FV infection in these low-recovery mice and showed that CD4+ T-helper cells are required for the Rfv-3-controlled FV antibody response.

* 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, November 1998, p. 9400-9403, Vol. 72, No. 11
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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