title: Accelerated programmed cell death of MRL-lpr/lpr T lymphocytes.
abstract: MRL-lpr/lpr (lpr) mice develop a polyclonal accumulation of abnormal peripheral T lymphocytes, which bear surface alpha beta TCR, CD3, and the B220 isoform of CD45, but lack CD4, CD8, and CD2. These T cells have a constitutively phosphorylated CD3 zeta chain and manifest a defect in signal transduction that results in a lack of IL-2 production and proliferation. We investigated whether this signaling abnormality might contribute to their accumulation via a defect in T cell elimination in the periphery. T cell deletion occurs through a process of programmed cell death with DNA degradation, or apoptosis. Viable lymphocytes from lpr mice were found to undergo rapid programmed cell death in culture within 4 h without additional activation, which was not observed in lymphocytes from normal MRL-+/+ or C57BL/6-+/+ mice. Both nonmature B220+ and mature B220- T lymphocytes from lpr mice display this accelerated programmed cell death, indicating that this is a defect affecting all peripheral T lymphocytes in lpr mice. In vitro apoptosis of lpr T cells could be inhibited with PMA, a stimulator of protein kinase C. Thus, the massive accumulation of T lymphocytes in the lymphoid tissue of lpr mice is not due to a defect in their ability to undergo programmed cell death in vitro. The activation state of lpr T cells may contribute to their rapid degradation of DNA in vitro.
authors.affiliation: Department of Medicine, University of Vermont, Burlington 05405.
authors.forename: N
authors.initials: N
authors.lastname: Van Houten
authors.forename: R C
authors.initials: RC
authors.lastname: Budd
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D002470:Cell Survival; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D008232:Lymphoproliferative Disorders / Q000276:immunology*; D051379:Mice; D011493:Protein Kinase C / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D004247:DNA; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate