Clonal deletion of postthymic T cells: veto cells kill precursor cytotoxic T lymphocytes

J Exp Med. 1992 Mar 1;175(3):863-8. doi: 10.1084/jem.175.3.863.

Abstract

Veto cell-mediated suppression of cytotoxic T lymphocyte (CTL) responses has been proposed as one mechanism by which self-tolerance is maintained in mature T cell populations. We have previously reported that murine bone marrow cells cultured in the presence of high-dose interleukin 2 (IL-2) (activated bone marrow cells [ABM]) mediate strong veto suppressor function. To examine mechanisms by which ABM may suppress precursor CTL (p-CTL) responses, we used p-CTL generated from spleen cells of transgenic mice expressing a T cell receptor specific for H-2 Ld. It was demonstrated that the cytotoxic response by these p-CTL after stimulation with irradiated H-2d/k spleen cells was suppressed by DBA/2 (H-2d) ABM, but not by B10.BR (H-2k) ABM or dm1 (Dd, Ld mutant) ABM. Flow cytometry analysis with propidium iodide staining revealed that these p-CTL were specifically deleted by incubation with H-2d ABM, but not with H-2k ABM. These data indicate that ABM veto cells kill p-CTL with specificity for antigens expressed on the surface of the ABM, and that the mechanism for veto cell activity of ABM is clonal deletion of p-CTL.

MeSH terms

  • Animals
  • Bone Marrow Cells
  • Clone Cells / immunology
  • Epitopes
  • Interleukin-2 / pharmacology
  • Lymphocyte Depletion
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Regulatory / physiology*

Substances

  • Epitopes
  • Interleukin-2