Homotypic interactions mediated through LFA-1/ICAM-3 decrease the proliferative response of activated T cells.
T cell activation occurs when the T cell receptor (TCR) is engaged by an antigen-MHC complex on the surface of an antigen-presenting cell (APC). Additional signals provided by accessory molecules serve to modulate this response. Independent of TCR engagement, treatment of T lymphocytes with a combination of phorbol ester and CD28 ligation will result in a proliferative response. This also induces homotypic adhesion mediated by LFA-l/ICAM interactions. We demonstrate that the prevention of homotypic interactions between T cells resulted in a two- to fivefold increase in the proliferative response. This occurred whether the homotypic interactions were prevented by blockade of LFA-1, by the use of plate immobilized antibodies against other cell surface molecules, or by culture at low cell density. We further demonstrate that the increased proliferation was a result of interference with a negative signal delivered to the T cell as a result of ICAM-3-mediated events. These data demonstrate LFA-1/ICAM-3 interactions between T cells in turn regulate an LFA-1-independent pathway that results in homotypic adhesion and a downregulation of the proliferative response of activated T cells.
Green
J M
JM
Department of Medicine, University of Chicago, Illnois 60637, USA.
Thompson
C B
CB
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D015703:Antigens, CD; D000943:Antigens, Differentiation; D001667:Binding, Competitive / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000378:metabolism / Q000502:physiology*; D004768:Enterotoxins / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism / Q000502:physiology*; D011940:Receptor Aggregation / Q000187:drug effects / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D000943:Antigens, Differentiation; D015815:Cell Adhesion Molecules; D004768:Enterotoxins; C483616:ICAM3 protein, human; D016169:Lymphocyte Function-Associated Antigen-1; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal; D013755:Tetradecanoylphorbol Acetate