Stimulation through intercellular adhesion molecule-1 provides a second signal for T cell activation.
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.
Chirathaworn
Chintana
C
Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA.
Kohlmeier
Jacob E
JE
Tibbetts
Scott A
SA
Rumsey
Lisa M
LM
Chan
Marcia A
MA
Benedict
Stephen H
SH
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*
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