Lymphokine regulation of activation-induced apoptosis in T cells of IL-2 and IL-2R beta knockout mice

Cell Immunol. 1998 May 1;185(2):158-63. doi: 10.1006/cimm.1998.1282.


Recent studies using IL-2R alpha knockout mice have generated conflicting results regarding the hypothesis that IL-2/IL-2R interaction is obligatory for the development of AICD, which plays a central and pivotal role in maintaining peripheral tolerance. A relevant consequence of AICD defect is the demonstrated development of autoimmune lymphoproliferative disease in IL-2, IL-2R alpha, and IL-2R beta knockout mice, but not in IL-4, IL-7, or IL-7R knockout mice. Whether IL-4, IL-7, or IL-15 can provide the required signal for AICD development is addressed here using IL-2 and IL-2R beta knockout mice. Lymph node T cells from knockout mice were stimulated with Con A plus rIL-1 for 3 days and then maintained in high concentrations of rIL-4, rIL-7, or rIL-15 for an additional 3 days before they were subjected to AICD analysis. Our study demonstrates that IL-4, IL-7, and IL-15 can transduce signals critical for AICD development in the absence of IL-2-mediated signals. The requirement for relatively high concentrations of these lymphokines suggests their limited role in maintaining peripheral T cell tolerance, thus explaining the differential expression of autoimmune lymphoproliferative disease in the targeted mutant strains described above.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / immunology*
  • Fas Ligand Protein
  • Interleukin-15 / genetics
  • Interleukin-15 / pharmacology
  • Interleukin-2 / deficiency
  • Interleukin-2 / genetics*
  • Interleukin-4 / genetics
  • Interleukin-4 / pharmacology
  • Interleukin-7 / genetics
  • Interleukin-7 / pharmacology
  • Ligands
  • Lymphocyte Activation* / drug effects
  • Lymphokines / physiology*
  • Membrane Glycoproteins / physiology
  • Mice
  • Mice, Knockout
  • Mice, SCID
  • Receptors, Interleukin-2 / deficiency
  • Receptors, Interleukin-2 / genetics*
  • Recombinant Proteins / pharmacology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • fas Receptor / physiology


  • Fas Ligand Protein
  • Fasl protein, mouse
  • Interleukin-15
  • Interleukin-2
  • Interleukin-7
  • Ligands
  • Lymphokines
  • Membrane Glycoproteins
  • Receptors, Interleukin-2
  • Recombinant Proteins
  • fas Receptor
  • Interleukin-4