CD28 and T cell antigen receptor signal transduction coordinately regulate interleukin 2 gene expression in response to superantigen stimulation.
Activation of an immune response requires intercellular contact between T lymphocytes and antigen-presenting cells (APC). Interaction of the T cell antigen receptor (TCR) with antigen in the context of major histocompatibility molecules mediates signal transduction, but T cell activation appears to require the induction of a second costimulatory signal transduction pathway. Recent studies suggest that interaction of CD28 with B7 on APC might deliver such a costimulatory signal. To investigate the role of CD28 signal transduction during APC-dependent T cell activation, we have used Staphylococcal enterotoxins (SEs) presented by a B7-positive APC. We used anti-B7 monoclonal antibodies and a mutant interleukin 2 (IL-2) promoter construct, unresponsive to CD28-generated signals, in transient transfection assays to examine the contribution of the CD28-B7 interaction to IL-2 gene activation. These studies indicate that the CD28-regulated signal transduction pathway is activated during SE stimulation of T cells and plays an important role in SE induction of IL-2 gene expression through its influence upon the CD28-responsive element contained within the IL-2 gene promoter. This effect is particularly profound in the activation of the IL-2 gene in peripheral blood T cells.
Fraser
J D
JD
Howard Hughes Medical Institute, University of California, San Francisco 94143.
Newton
M E
ME
Weiss
A
A
D000938:Antigen-Presenting Cells / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D015703:Antigens, CD / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D018106:CD28 Antigens; D004768:Enterotoxins / Q000276:immunology*; D004790:Enzyme Induction; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000235:genetics*; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism
D000942:Antigens, Bacterial; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D004768:Enterotoxins; D007376:Interleukin-2; D009687:Nuclear Proteins; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; C019368:enterotoxin D, Staphylococcal; D010738:Type C Phospholipases