Primed T cells are more resistant to Fas-mediated activation-induced cell death than naive T cells.
Memory T cells respond in several functionally different ways from naive T cells and thus function as efficient effector cells. In this study we showed that primed T cells were more resistant to Fas-mediated activation-induced cell death (AICD) than naive T cells using OVA-specific TCR transgenic DO10 mice and Fas-deficient DO10 lpr/lpr mice. We found that apoptosis was efficiently induced in activated naive T cells at 48 and 72 h after Ag restimulation (OVA peptide; 0.3 and 3 microM), whereas apoptosis was not significantly increased in activated primed T cells at 24-72 h after Ag restimulation. We further showed that the resistance to AICD in primed T cells was due to the decreased sensitivity to apoptosis induced by Fas-mediated signals, but TCR-mediated signaling equally activated both naive and primed T cells to induce Fas and Fas ligand expressions. Furthermore, we demonstrated that primed T cells expressed higher levels of Fas-associated death domain-like IL-1beta-converting enzyme inhibitory protein (FLIP), an inhibitor of Fas-mediated apoptosis, at 24-48 h after Ag restimulation than naive T cells. In addition, Bcl-2 expression was equally observed between activated naive and primed T cells after Ag restimulation. Thus, these results indicate that naive T cells are sensitive to Fas-mediated AICD and are easily deleted by Ag restimulation, while primed/memory T cells express higher levels of FLIP after Ag restimulation, are resistant to Fas-mediated AICD, and thus function as efficient effector cells for a longer period.
Department of Internal Medicine II, Chiba University School of Medicine, Japan.
M
M
Inaba
K
K
Kurasawa
M
M
Mamura
K
K
Kumano
Y
Y
Saito
I
I
Iwamoto
D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins / Q000096:biosynthesis; D002478:Cells, Cultured; D053222:Fas Ligand Protein; D007113:Immunity, Innate; D007114:Immunization; D016130:Immunophenotyping; D007274:Injections, Intraperitoneal; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D019463:Mice, Inbred MRL lpr; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D019014:fas Receptor / Q000096:biosynthesis / Q000502:physiology*
D000941:Antigens; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins; C506387:Cflar protein, mouse; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D010047:Ovalbumin