T cell receptor/CD3 and CD28 use distinct intracellular signaling pathways

✍ Scribed by René A. W. Van Lier; Miranda Brouwer; Els De Groot; Ijsbrand Kramer; Lucien A. Aarden; Arthur J. Verhoeven

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: English
• Weight: 385 KB
• Volume: 21
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.1830210731

✦ Synopsis

T cell receptodCD3 and CD28 use distinct intracellular signaling pathways*

Ligation of the T cell membrane antigen CD28 strongly enhances cytokine secretion in humanT lymphocytes that are activated viaTcell receptor (TcR)/CD3 or CD2 molecules.This study was undertaken to investigate whether, as has been indicated for activation via TcR/CD3, stimulation via CD28 is dependent on the activation of protein kinase C (PKC). Two inhibitors of PKC, l-alkyl 2methyl-glycerol and staurosporine, caused a dose-dependent inhibition of Tcell proliferation induced by anti-CD3 monoclonal antibodies (mAb). The induction of interleukin (IL) 2 secretion was found to be more sensitive to the effects of the PKC inhibitors than the up-regulation of IL2 receptor expression. In marked contrast, the anti-CD28 mAb-mediated enhancement of Tcell proliferation and IL 2 secretion were insensitive to the action of either compound.We conclude that two independent signaling pathways may be operational in humanTcells.The first used by TcR/CD3 depends on the activation of PKC, whereas the second is employed by CD28 and functions independently of PKC.