title: T cell receptor/CD3 and CD28 use distinct intracellular signaling pathways.
abstract: Ligation of the T cell membrane antigen CD28 strongly enhances cytokine secretion in human T lymphocytes that are activated via T cell 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, 1-alkyl 2-methyl-glycerol and staurosporine, caused a dose-dependent inhibition of T cell 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 IL 2 receptor expression. In marked contrast, the anti-CD28 mAb-mediated enhancement of T cell proliferation and IL 2 secretion were insensitive to the action of either compound. We conclude that two independent signaling pathways may be operational in human T cells. The first used by TcR/CD3 depends on the activation of PKC, whereas the second is employed by CD28 and functions independently of PKC.
authors.affiliation: Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, University of Amsterdam, The Netherlands.
authors.forename: R A
authors.initials: RA
authors.lastname: Van Lier
authors.forename: M
authors.initials: M
authors.lastname: Brouwer
authors.forename: E D
authors.initials: ED
authors.lastname: De Groot
authors.forename: I
authors.initials: I
authors.lastname: Kramer
authors.forename: L A
authors.initials: LA
authors.lastname: Aarden
authors.forename: A J
authors.initials: AJ
authors.lastname: Verhoeven
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D015703:Antigens, CD / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D018106:CD28 Antigens; D017252:CD3 Complex; D006801:Humans; D008213:Lymphocyte Activation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D019311:Staurosporine; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000470:Alkaloids; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell; D011493:Protein Kinase C; D019311:Staurosporine