title: ICAM-3 (CD50) cross-linking augments signaling in CD3-activated peripheral human T lymphocytes.
abstract: ICAM-3 is a pan-hematopoietic, constitutive adhesion molecule. ICAM-3 binds to LFA-1 on antigen-presenting cells (APC) stabilizing the T cell-APC interaction, facilitating signaling through the CD3/TCR complex. However, recent evidence using cultured and transformed T cells suggests ICAM-3 may also function in signaling. Because ICAM-3 is constitutively expressed on resting T cells, we postulated that signaling through ICAM-3 in resting T cells represents an important costimulatory mechanism in these cells. In purified resting human T cells, cross-linking both ICAM-3 and CD3 with plate-bound antibodies resulted in a marked increase in cell size (consistent with blastogenesis), synergistically increased surface expression of CD25 and CD69, and increased T cell metabolism. Similarly, concomitant ICAM-3 and CD3 stimulation significantly (P < 0.001) increased resting human T cell phosphatidylinositol hydrolysis and phospholipase C-gamma1 phosphorylation. These results indicate that ICAM-3 augments signaling through CD3, functioning as a costimulatory molecule for resting T cells in the initial activation step.
authors.affiliation: Department of Medicine, Center of Excellence for Arthritis and Rheumatology, Louisiana State University School of Medicine at Shreveport, 71130-3932, USA. sberne@lsumc.edu
authors.forename: S M
authors.initials: SM
authors.lastname: Berney
authors.forename: T
authors.initials: T
authors.lastname: Schaan
authors.forename: J S
authors.initials: JS
authors.lastname: Alexander
authors.forename: G
authors.initials: G
authors.lastname: Peterman
authors.forename: P A
authors.initials: PA
authors.lastname: Hoffman
authors.forename: R E
authors.initials: RE
authors.lastname: Wolf
authors.forename: H
authors.initials: H
authors.lastname: van der Heyde
authors.forename: T P
authors.initials: TP
authors.lastname: Atkinson
mesh_terms: D015703:Antigens, CD; D000943:Antigens, Differentiation; D017252:CD3 Complex / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D008213:Lymphocyte Activation / Q000276:immunology; D008564:Membrane Potentials; D010716:Phosphatidylinositols / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D003432:Cross-Linking Reagents; C483616:ICAM3 protein, human; D010716:Phosphatidylinositols; D010738:Type C Phospholipases