Selective activation-induced apoptosis of peripheral T cells imposed by macrophages. A potential mechanism of antigen-specific peripheral lymphocyte deletion
| Autor: | Dh, Munn, Joseph Pressey, Ac, Beall, Hudes R, Alderson MR |
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| Předmět: |
Macrophage Colony-Stimulating Factor
Macrophages Cell Cycle Antibodies Monoclonal Clonal Deletion Apoptosis Autoimmunity Cell Differentiation Lymphocyte Activation Coculture Techniques Recombinant Proteins Interferon-gamma Self Tolerance Proto-Oncogene Proteins c-bcl-2 T-Lymphocyte Subsets Proto-Oncogene Proteins Cytokines Humans fas Receptor Cells Cultured |
| Zdroj: | Europe PubMed Central |
| Popis: | The self-reactive T cells that escape clonal deletion in the thymus must be suppressed by the less well characterized process of peripheral tolerance. In this study, we show that monocyte-derived macrophages (M phi) undergoing terminal differentiation in the presence of macrophage CSF (M-CSF) acquire the ability to selectively induce apoptosis of T cells in an activation-specific fashion. Lymphocytes were stimulated via the TCR using anti-CD3 cross-linking, staphylococcal superantigen, or allogeneic mixed-leukocyte cultures. T cells activated while in contact with M-CSF-derived M phi exited the resting G0 state and re-entered the cell cycle, but experienced a sustained arrest near the first G1/S transition, followed by progressive apoptosis. In contrast, lymphocytes that were not stimulated remained viable, and could later activate normally when removed from contact with M phi. Functionally, exposure of T cells to alloantigens presented by M-CSF-derived M phi resulted in a selective depletion of the alloresponsive T cell population, while preserving reactivity to other mitogens and to alloantigens from different donors. The ability of M phi to impose activation-induced apoptosis on lymphocytes was regulated developmentally, being absent in fresh monocytes, progressively acquired during differentiation in M-CSF, and abrogated if monocytes were exposed to IFN-gamma before differentiation. We speculate that this novel interaction may help to selectively delete autoreactive T cells that respond to self Ags presented by noninflammatory tissue M phi. |
| Databáze: | OpenAIRE |
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