title: T cell receptor stimulation, but not CD28 costimulation, is dependent on LFA-1-mediated events.
abstract: Accessory molecules play a crucial role in the development of the T cell response to antigenic challenge. In this manuscript we specifically examine the role of two accessory molecules, CD28 and LFA-1, in modulating the T cell proliferative response to a variety of stimuli. We demonstrate that the proliferation induced by staphylococcal enterotoxins A and B in combination with CD28 costimulation is dependent on LFA-1-mediated events. This requirement for LFA-1 is independent of T cell-accessory cell adhesion. Similarly, an allogeneic mixed lymphocyte reaction, which has previously been shown to be a CD28-dependent response, can be inhibited by blockade of LFA-1. This suggests LFA-1 plays an essential role in these responses, either by enhancing intercellular adhesion or by an independent signal transduction event. In contrast, when the primary activating stimulus is delivered by immobilized anti-CD3 antibody or by PMA, and the secondary stimulus by either alpha-CD28 or cell-bound CD28 ligand B7, there is no requirement for LFA-1. In addition, we demonstrate that cross-linking of LFA-1 with immobilized monoclonal antibody, or engagement of LFA-1 with ICAM-1 expressed on the surface of a CHO cell, provide an insufficient costimulus for T cell proliferation initiated by enterotoxin, immobilized alpha-CD3 or phorbol ester. Our data suggests that LFA-1, in contrast to CD28, functions not as a costimulatory molecule, but serves primarily to modulate the signal delivered through the T cell receptor.
authors.affiliation: Department of Internal Medicine and Microbiology, University of Michigan Medical Center, Ann Arbor 48109.
authors.forename: J M
authors.initials: JM
authors.lastname: Green
authors.forename: X G
authors.initials: XG
authors.lastname: Zheng
authors.forename: Y
authors.initials: Y
authors.lastname: Shimizu
authors.forename: C B
authors.initials: CB
authors.lastname: Thompson
authors.forename: L A
authors.initials: LA
authors.lastname: Turka
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D018122:B7-1 Antigen / Q000502:physiology; D018821:CD18 Antigens; D018106:CD28 Antigens / Q000502:physiology*; D017252:CD3 Complex / Q000502:physiology; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000502:physiology; D006224:Cricetinae; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D008024:Ligands; D008213:Lymphocyte Activation / Q000502:physiology; D007959:Lymphocyte Culture Test, Mixed / Q000379:methods; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D018089:Superantigens / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D018821:CD18 Antigens; D018106:CD28 Antigens; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1; D011948:Receptors, Antigen, T-Cell; D018089:Superantigens; D018799:Intercellular Adhesion Molecule-1; D013755:Tetradecanoylphorbol Acetate