Deletion of CD4+ T cells and thymocytes by apoptosis in mouse mammary tumor virus (C4)-infected V beta 2 transgenic mice.
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.
Wang
H
H
E. Walter Albachten Department of Immunology, MCF-Prentis Comprehensive Cancer Center, Detroit, MI.
Gill
R F
RF
Lichlyter
D
D
Iglesias
A
A
Bluethmann
H
H
Wei
W Z
WZ
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology*; D004249:DNA Damage; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006410:Hematopoiesis; D008297:Male; D008324:Mammary Tumor Virus, Mouse / Q000472:pathogenicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013950:Thymus Gland / Q000473:pathology*; D014412:Tumor Virus Infections / Q000276:immunology / Q000473:pathology*
D017931:DNA Primers; D016693:Receptors, Antigen, T-Cell, alpha-beta