Requirement for CD4(+) T cells in the Friend murine retrovirus neutralizing antibody response: evidence for functional T cells in genetic low-recovery mice.
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 x A/Wy)F1 mice, which have the H-2(a/a) Rfv-3(r/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.
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA.
H J
HJ
Super
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Brooks
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Hasenkrug
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Chesebro
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005622:Friend murine leukemia virus / Q000276:immunology*; D006183:H-2 Antigens / Q000235:genetics; D007075:Immunoglobulin M / Q000096:biosynthesis; D066298:In Vitro Techniques; D007942:Leukemia, Experimental / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D012192:Retroviridae Infections / Q000235:genetics / Q000276:immunology; D014412:Tumor Virus Infections / Q000235:genetics / Q000276:immunology; D014766:Viremia / Q000235:genetics / Q000276:immunology
D000914:Antibodies, Viral; D006183:H-2 Antigens; D007075:Immunoglobulin M