Lymphokine regulation of activation-induced apoptosis in T cells of IL-2 and IL-2R beta knockout mice.
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.
Kung
J T
JT
Institute of Molecular Biology, Academic Sinica, Taipei, Taiwan.
Beller
D
D
Ju
S T
ST
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D053222:Fas Ligand Protein; D019409:Interleukin-15 / Q000235:genetics / Q000494:pharmacology; D007376:Interleukin-2 / Q000172:deficiency / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics / Q000494:pharmacology; D015851:Interleukin-7 / Q000235:genetics / Q000494:pharmacology; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects; D008222:Lymphokines / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D015375:Receptors, Interleukin-2 / Q000172:deficiency / Q000235:genetics*; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019014:fas Receptor / Q000502:physiology
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D019409:Interleukin-15; D007376:Interleukin-2; D015851:Interleukin-7; D008024:Ligands; D008222:Lymphokines; D008562:Membrane Glycoproteins; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D019014:fas Receptor; D015847:Interleukin-4