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  • Title: Deletion of CD4+ T cells and thymocytes by apoptosis in mouse mammary tumor virus (C4)-infected V beta 2 transgenic mice.
    Author: Wang H, Gill RF, Lichlyter D, Iglesias A, Bluethmann H, Wei WZ.
    Journal: Eur J Immunol; 1994 Dec; 24(12):2950-6. PubMed ID: 7805721.
    Abstract:
    Mouse mammary tumor virus MMTV (C4) encodes a V beta 2-specific superantigen. In V beta 2 transgenic (TG2) mice more than 98% of peripheral T cells express V beta 2. Infection of Tg2 mice with MMTV (C4) at birth through their mothers' milk or at 6-8 weeks of age by intravenous injection resulted in massive deletion of peripheral CD4+ T cells and suppressed thymopoiesis. The number of peripheral CD8+ T cells was not affected in neonatally infected mice. In older mice injected with MMTV (C4), splenic CD8+ T cells were significantly elevated. Suppressed thymopoiesis was observed in both neonatally infected and older mice injected with MMTV (C4). Thymocytes which expressed high level CD3 or V beta 2 were deleted. To determine if T cells or thymocytes were deleted through apoptosis, DNA fragmentation was examined by flow cytometry and diphenylamine (DPA) binding assay. Approximately 31% of CD4+ T cells from MMTV (C4)-infected Tg2 mice as compared to 6% from normal Tg2 mice contained fragmented nuclear DNA by flow-cytometric analysis. The DPA binding assay showed significantly increased total soluble DNA in lymph node cells and thymocytes from MMTV (C4)-infected mice. The kinetics of T cell and thymocyte apoptosis correspond to their deletion, supporting apoptosis as the mechanism of T cell and thymocyte deletion. CD4+ T cell and thymocyte deletion by MMTV (C4) in Tg2 mice provides a sensitive system for the analysis of retrovirus superantigen-induced apoptosis.
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