ABSTRACT
Spontaneous resorption in the CBA x DBA/2 model is attributed to NK cells, macrophages, and Th1-type cytokines. In vivo depletion of NK cells by anti-asialoGM1 Ab or macrophage depletion by silicon dioxide treatment reduced abortion rates, which could no longer be boosted by injecting TNF-alpha (which activates NK cells) or IFN-gamma (which activates macrophages). TNF-alpha + gamma-IFN coadministration aborted >80% of the embryos whether or not NK cells or macrophages had been depleted or estradiol + progesterone was injected to correct potential reduction in ovarian function by cytokines. The cytokines also aborted IRF1+/+ C57BL/6 but not IRF1-/- females pregnant by IRF1+/+ DBA/2. Both spontaneous and cytokine-boosted abortions in CBA x DBA/2 were blocked by Ab to fgl2 prothrombinase [corrected] expressed by cytokine-stimulated vascular endothelial cells and monocytes; in vivo Ab depletion of granulocytes also prevented TNF-alpha + IFN-gamma-induced abortions. Cytokine-triggered thrombotic/inflammatory processes in maternal uteroplacental blood vessels causes abortion.
Subject(s)
Abortion, Spontaneous/immunology , Cytokines/physiology , Fibrinogen , Killer Cells, Natural/immunology , Thromboplastin/physiology , Abortion, Spontaneous/genetics , Abortion, Spontaneous/prevention & control , Animals , Crosses, Genetic , Cytokines/genetics , DNA-Binding Proteins/genetics , Endothelium, Vascular/immunology , Endothelium, Vascular/pathology , Female , Granulocytes/immunology , Immune Sera/administration & dosage , Injections, Intraperitoneal , Interferon Regulatory Factor-1 , Interferon-gamma/administration & dosage , Macrophages/immunology , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , Mice, Inbred DBA , Mice, Knockout , Phosphoproteins/genetics , Pregnancy , Thromboplastin/immunologyABSTRACT
CD30 is found on Reed-Sternberg cells of Hodgkin's disease and on a variety of non-Hodgkin's lymphoma cells and is up-regulated on cells after Epstein-Barr virus, human T cell leukemia virus, and HIV infections. We report here that the thymus in CD30-deficient mice contains elevated numbers of thymocytes. Activation-induced death of thymocytes after CD3 cross-linking is impaired both in vitro and in vivo. Breeding the CD30 mutation separately into alpha beta TCR-or gamma delta TCR-transgenic mice revealed a gross defect in negative but not positive selection. Thus, like TNF-receptors and Fas/Apo-1, the CD30 receptor is involved in cell death signaling. It is also an important coreceptor that participates in thymic deletion.
