Activation-induced elimination of peripheral t cells by mcsf-derived macrophages (M08)

D. H. Mann, J. T. Attwood, A. L. Mellor

Research output: Contribution to journalArticle

Abstract

We have recently shown that human monocyte-derived Mfs exposed to macrophage colony-stimulating factor (MCSF) acquire the ability to induce apoptoais of T cells activated via T cell receptor (TOR) cross linking (J Immunol 156:523). We now employ a model using tranegenic mice to ask whether this novel phenomenon also occurs when T cells recognize antigen presented by MCSF-derived MøB. Mice were constructed on a H2Kk background which were either transgenic for a TCR recognizing H2Kb, or tranagenie for the H2Kb antigen itself. T cells from TCR-transgenic mice were cultured with MCSF-derived M#a expressing the target antigen. Under these conditions the T cells exited the resting state ae indicated by morphologic blastogenesisf but experienced uniform (>95%) cell cycle arrest near the Gl/S boundary. Arrested T cells progressively diad over the next 48-72 hrs without proceeding further through the cell cycle. MCSF-derived M$s that did not express the target antigen did not cause T cell death/ indicating that elimination of T cells required recognition of antigen. Furthermore/ in mixed co-culture experiments/ TCR-transgenic T cells were progressively eliminated while T cells that were not TCR-transgenic were spared, showing that Mip-mediated cell death was selective. Cell death waa not initiated by the fas/fas ligand system, since Møs from fas ligand-deficiant gId mice were fully suppreesive for T cells. We thus describe a novel mechanism whereby MCSF-derived Ms can selectively delete T cells which recognize antigens they present. Since tissue MøS normally present self antigens, we speculate that this mechanism may contribute to peripheral T cell tolerance.

Original languageEnglish (US)
Pages (from-to)A1458
JournalFASEB Journal
Volume10
Issue number6
StatePublished - Dec 1 1996

Fingerprint

T-cells
Macrophages
Chemical activation
T-Lymphocytes
Macrophage Colony-Stimulating Factor
Antigens
Cell death
Fas Ligand Protein
Cell Death
Cells
Autoantigens
Coculture Techniques
T-Cell Antigen Receptor
Cell Cycle Checkpoints
Cell culture
Transgenic Mice
Monocytes
Cell Cycle

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Mann, D. H., Attwood, J. T., & Mellor, A. L. (1996). Activation-induced elimination of peripheral t cells by mcsf-derived macrophages (M08). FASEB Journal, 10(6), A1458.

Activation-induced elimination of peripheral t cells by mcsf-derived macrophages (M08). / Mann, D. H.; Attwood, J. T.; Mellor, A. L.

In: FASEB Journal, Vol. 10, No. 6, 01.12.1996, p. A1458.

Research output: Contribution to journalArticle

Mann, DH, Attwood, JT & Mellor, AL 1996, 'Activation-induced elimination of peripheral t cells by mcsf-derived macrophages (M08)', FASEB Journal, vol. 10, no. 6, pp. A1458.
Mann, D. H. ; Attwood, J. T. ; Mellor, A. L. / Activation-induced elimination of peripheral t cells by mcsf-derived macrophages (M08). In: FASEB Journal. 1996 ; Vol. 10, No. 6. pp. A1458.
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