The insulin-like growth factor-I receptor is regulated by CD28 and protects activated T cells from apoptosis.
Co-stimulatory signals through the CD28 receptor enhance the survival of T cells that have their antigen receptor (TCR) engaged. Here we show that stimulation through the CD28 receptor in the absence of TCR engagement with either an anti-CD28 cross-linking antibody or the CD80 ligand transiently increases expression of the insulin-like growth factor-I receptor (IGF-IR) on T cells. Antibodies that block signaling through the IGF-IR decrease the survival of T cells activated through the TCR and CD28 in the presence of IL-2 by more than 50%, and also enhance susceptibility to Fas-induced apoptosis. CD28 stimulation increases IGF-IR expression on Jurkat cells, and exogenously added IGF-I can protect these cells from Fas-induced apoptosis. We conclude that CD28-mediated enhancement of IGF-IR expression provides activated T cells with essential survival signals that are independent of survival mediated by IL-2 and Bcl-xl.
Walsh
P T
PT
Cell Biology Laboratory, Department of Biochemistry, University College Cork, Lee Maltings, Cork, Ireland.
O'Connor
R
R
D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D018122:B7-1 Antigen / Q000378:metabolism; D015153:Blotting, Western; D018106:CD28 Antigens / Q000276:immunology* / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007376:Interleukin-2 / Q000276:immunology; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D011940:Receptor Aggregation / Q000187:drug effects; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051020:bcl-X Protein; D019014:fas Receptor / Q000502:physiology
D000906:Antibodies; D018122:B7-1 Antigen; C494811:BCL2L1 protein, human; D018106:CD28 Antigens; D017252:CD3 Complex; D007376:Interleukin-2; D019253:Proto-Oncogene Proteins c-bcl-2; D011948:Receptors, Antigen, T-Cell; D051020:bcl-X Protein; D019014:fas Receptor; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1