title: Stimulation through intercellular adhesion molecule-1 provides a second signal for T cell activation.
abstract: Regulation of T cell activation requires two signals. First, appropriately presented Ag in the context of MHC interacts with the T cell Ag receptor-CD3 complex. The best-studied second signal is CD28, which resides on the T cell and responds to its counter receptor, B7. A second signal also can be delivered through LFA-1 residing on the T cell, responding to its counter receptor ICAM-1 residing on a different cell. Characterization of a second signal is tied to its ability to costimulate (along with stimulation through the TCR) proliferation, IL-2 secretion, and coactivation of phosphatidylinositol 3-kinase. We examined whether ICAM-1, residing on the T cell surface, could deliver a second signal into that T cell. Costimulation through CD3 plus ICAM-1 caused increased T cell proliferation, increased expression of the activation marker CD69, increased transcription through the IL-2 regulatory region, and increased secretion of selected Th1 but not Th2 cytokines. Costimulation through CD3 plus ICAM-1 caused synergistic activation of phosphatidylinositol 3-kinase. Finally, the combination of anti-CD3 plus anti-ICAM-1 (but not anti-CD3 alone) caused prolonged proliferation of naive T cells in a manner similar to costimulation through LFA-1 or CD28. Thus, we demonstrate for the first time that ICAM-1 resident on a T cell can deliver a costimulatory signal into that T cell.
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA.
authors.forename: Chintana
authors.initials: C
authors.lastname: Chirathaworn
authors.forename: Jacob E
authors.initials: JE
authors.lastname: Kohlmeier
authors.forename: Scott A
authors.initials: SA
authors.lastname: Tibbetts
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Rumsey
authors.forename: Marcia A
authors.initials: MA
authors.lastname: Chan
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Benedict
mesh_terms: D018106:CD28 Antigens / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D007376:Interleukin-2 / Q000235:genetics; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018106:CD28 Antigens; D016207:Cytokines; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D019869:Phosphatidylinositol 3-Kinases