T cell sensitivity to HLA class I-mediated apoptosis is dependent on interleukin-2 and interleukin-4

Eur J Immunol. 1997 Feb;27(2):495-9. doi: 10.1002/eji.1830270221.


Antibody interaction with a specific epitope of the HLA class I alpha1 domain triggers apoptosis of activated but not resting T and B cells by a pathway which involves neither Fas ligand nor tumor necrosis factor-alpha. We have investigated at which stage of activation and proliferation T cells become sensitive to HLA class I-mediated apoptosis, using two monoclonal antibodies (mAb) which recognize the same monomorphic epitope of the HLA class I alpha1 domain (mAb9O, mouse IgG1, and YTH862, rat IgG2b) and can induce apoptosis of phytohemagglutinin (PHA)-activated peripheral blood lymphocytes. Sensitivity to apoptosis develops after the expression of G1 markers (CD69 expression) but it is accelerated by addition of recombinant interleukin-2 (rIL-2). Blocking the IL-2 pathway by cyclosporin A, FK506, rapamycin, anti-IL-2 or CD25 antibodies, prevented the development of sensitivity to apoptosis. Addition of IL-2 and, to a lesser extent, IL-4, reversed the inhibitory effect of cyclosporin A. Conversely, rIL-7 and recombinant interferon-gamma restored proliferation of peripheral blood lymphocytes stimulated by PHA in the presence of cyclosporin A but did not restore sensitivity to class I-mediated apoptosis. Finally cells stimulated in the presence of the DNA polymerase inhibitor aphidicolin did not enter into S phase of the cell cycle but secreted IL-2 and underwent apoptosis when exposed to mAb90 or YTH862. Together, the data indicate that sensitivity of peripheral T cells to HLA class I-mediated apoptosis depends on both activation signals and IL-2 or IL-4, but does not require cell proliferation. These data suggest that YTH862 and mAb90 might be used for achieving clonal deletion of antigen-activated peripheral T cells in vivo, provided that the IL-2 pathway is not blocked by other immunosuppressive agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology*
  • Apoptosis / drug effects*
  • Clonal Deletion / drug effects
  • Drug Synergism
  • HLA Antigens / genetics
  • HLA Antigens / pharmacology*
  • HLA-A Antigens / genetics
  • HLA-A Antigens / pharmacology
  • HLA-B Antigens / genetics
  • HLA-B Antigens / pharmacology
  • HLA-C Antigens / genetics
  • HLA-C Antigens / pharmacology
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / pharmacology*
  • Humans
  • Interferon-gamma / pharmacology
  • Interleukin-2 / pharmacology*
  • Interleukin-4 / pharmacology*
  • Interleukin-7 / pharmacology
  • Lymphocyte Activation / immunology
  • T-Lymphocytes / drug effects*


  • Antibodies, Monoclonal
  • HLA Antigens
  • HLA-A Antigens
  • HLA-B Antigens
  • HLA-C Antigens
  • Histocompatibility Antigens Class I
  • Interleukin-2
  • Interleukin-7
  • Interleukin-4
  • Interferon-gamma