Genetic analysis of the effects of Mtv-2 on the T cell repertoire in the WXG-2 mouse strain.
In this report, the T cell repertoire was studied in a natural genetic model system using a novel mouse strain (WXG-2) carrying a single pathogenic mouse mammary tumor virus (MMTV) provirus (Mtv-2) on an otherwise MMTV-free genetic background. The Mtv-2 provirus has complete biological activity, produces infectious milk-transmitted virus, and contributes to mammary carcinogenesis by an insertion mutation mechanism. In mice carrying the Mtv-2 provirus, T cells expressing V beta 14 were specifically deleted in mice with a functional MHC class II I-E gene but not in I-E- controls. The deletion of V beta 14+ T cells was more rapid in mice with the Mtv-2 provirus than in Mtv-2-free control mice infected with exogenous MMTV. In addition, the Mtv-2 deletion phenotype was age dependent. A slow depletion of V beta 14+ T cells was observed, and greater than 95% of the V beta 14+ T cells were eliminated by 6 months of age. These experiments indicate that (i) the Mtv-2 provirus encodes or regulates expression of a V beta 14-specific superantigen, (ii) interactions between Mtv-2 and other MMTV proviruses are not necessary for the V beta 14 deletion phenotype, (iii) the presence of a retroviral superantigen in all cells is not sufficient for T cell depletion during neonatal development in the thymus, and (iv) the Mtv-2 provirus and its associated exogenous provirus have the same V beta specificity.(ABSTRACT TRUNCATED AT 250 WORDS)
Ferrick
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DA
Department of Veterinary Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis 95616.
Cho
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K
Gemmell-Hori
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Morris
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DW
D000818:Animals; D001483:Base Sequence; D004279:DNA, Viral / Q000235:genetics; D008325:Mammary Neoplasms, Experimental / Q000209:etiology / Q000235:genetics / Q000276:immunology; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D011533:Proviruses / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D004279:DNA, Viral