DELETION OF CD4(-CELLS AND THYMOCYTES BY APOPTOSIS IN MOUSE MAMMARY-TUMOR VIRUS (C4)-INFECTED V-BETA-2 TRANSGENIC MICE() T)

Mouse mammary tumor virus MMTV(C4) encodes a V beta 2-specific superan tigen. 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 inj ection resulted in massive deletion of peripheral CD4+ T cells and sup pressed thymopoiesis. The number of peripheral CD8+ T cells was not af fected in neonatally infected mice. In older mice injected with MMTV(C 4), splenic CD8+ T cells were significantly elevated. Suppressed thymo poiesis was observed in both neonatally infected and older mice inject ed with MMTV(C4). Thymocytes which expressed high level CD3 or V beta 2 were deleted. To determine if T cells or thymocytes were deleted thr ough apoptosis, DNA fragmentation was examined by now cytometry and di phenylamine (DPA) binding assay. Approximately 31% of CD4+ T cells fro m MMTV(C4)-infected Tg2 mice as compared to 6% from normal Tg2 mice co ntained fragmented nuclear DNA by now-cytometric analysis. The DPA bin ding assay showed significantly increased total soluble DNA in lymph n ode cells and thymocytes from MMTV(C4)-infected mice. The kinetics of T cell and thymocyte apoptosis correspond to their deletion, supportin g apoptosis as the mechanism of T cell and thymocyte deletion. CD4+ T cell and thymocyte deletion by MMTV(C4) in Tg2 mice provides a sensiti ve system for the analysis of retrovirus superantigen-induced apoptosi s.