The MAP kinases are differently utilized by CD28 and CD2 adhesion pathways in superantigen-activated Jurkat T cells

• Published in: Biological research Vol. 36; no. 2; pp. 263 - 278
• Main Authors: Visse, Edward, Inostroza, Juan, Cabello, Gertrudis, Parra, Eduardo
• Format: Journal Article
• Language: English
• Published: England Sociedad de Biología de Chile 2003; BMC
• Subjects: Animals; B7-1 Antigen - pharmacology; BIOLOGY; c-Jun N-terminal kinase; CD2 Antigens - immunology; CD28 Antigens - immunology; CD28 response element; CD58 Antigens - pharmacology; CHO Cells; Clinical Medicine; Cricetinae; Enterotoxins - immunology; Enzyme Activation; extracellular; Extracellular signal regulated kinase; Humans; Interleukin-2; Interleukin-2 - metabolism; JNK Mitogen-Activated Protein Kinases; Jurkat Cells - immunology; Jurkat Cells - physiology; Kirurgi; Klinisk medicin; Lymphocyte Activation; MAP Kinase Kinase 4; Medical and Health Sciences; Medicin och hälsovetenskap; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase Kinases - metabolism; Mitogen-Activated Protein Kinases - immunology; Mitogen-Activated Protein Kinases - metabolism; Mitogen-Activated Protein Kinases - physiology; Neurologi; Neurology; p38 Mitogen-Activated Protein Kinases; signal regulated kinase; Staphylococcal Enterotoxin A-E; Surgery; c-Jun N-terminal kinase; Interleukin-2; CD28 response element; Extracellular signal regulated kinase; Staphylococcal Enterotoxin A-E
• ISSN: 0716-9760; 0717-6287; 0716-9760; 0717-6287
• DOI: 10.4067/S0716-97602003000200016

To mimic the two-signal requirements for T cell activation mediated by ligands, we exposed the superantigens SEA or SEE (signal 1) to T cells incubated with HLA-DR/LFA-3 or HLA-DR/B7-1-CHO transfected cells (signal 2). LFA-3 costimulation was able to induce T cell proliferation as well as IFN-gamma and IL-4 production at similar levels as in cells induced by B7-1. Analysis of the CD28RE of the IL-2 promoter showed specific transcription factor recruitment at the CD28RE element upon induction by B7-1/SEE. Further functional studies with an IL-2 enhancer-promoter carrying either wild type or mutated versions of the CD28RE site revealed that this element is necessary for full activation upon B7-1 costimulation. While both CD28/B7-1 and CD2/LFA-3 costimulation resulted in the up-regulation of IL-4 and IFN-gamma promoters, IL-2 promoter activity and production of IL-2 were only seen after B7-1 costimulation. However, contrary to what has been previously proposed, we show that costimulation with either B7-1 or LFA-3 further enhanced the ERK-2 activity and strongly activated the p38 MAPK pathway, but only B7-1 costimulation induced high levels of JNK-1 activity. These data suggest that the differential effect of CD28 vs. CD2 can be related to the difference in the ability of the two pathways to induce JNK-1 activity.