Selective activation-induced apoptosis of peripheral T cells imposed by macrophages: A potential mechanism of antigen-specific peripheral lymphocyte deletion

David H Munn, Joseph Pressey, Arthur C. Beall, Richard Hudes, Mark R. Alderson

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Abstract

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 (MΦ) 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 Mφ 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 Mφ. Functionally, exposure of T cells to alloantigens presented by M-CSF-derived Mφ 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 Mφ 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-γ 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 Mφ.

Original languageEnglish (US)
Pages (from-to)523-532
Number of pages10
JournalJournal of Immunology
Volume156
Issue number2
StatePublished - Jan 15 1996

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Macrophages
Lymphocytes
Apoptosis
T-Lymphocytes
Antigens
Macrophage Colony-Stimulating Factor
Isoantigens
Monocytes
Clonal Deletion
Peripheral Tolerance
Superantigens
Mitogens
Thymus Gland
Cell Cycle
Leukocytes
Population

ASJC Scopus subject areas

  • Immunology

Cite this

Selective activation-induced apoptosis of peripheral T cells imposed by macrophages : A potential mechanism of antigen-specific peripheral lymphocyte deletion. / Munn, David H; Pressey, Joseph; Beall, Arthur C.; Hudes, Richard; Alderson, Mark R.

In: Journal of Immunology, Vol. 156, No. 2, 15.01.1996, p. 523-532.

Research output: Contribution to journalArticle

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