Differential activation-dependent regulation of integrin function in cultured human T-leukemic cell lines.
T lymphocytes isolated from human peripheral blood express beta 1 (VLA) and LFA-1 integrins, but strong binding to integrin ligands occurs only after the delivery of an activation stimulus to the T cell. To gain further insight into activation-dependent regulation of integrin function, we have analyzed integrin activity on three different T-leukemic cell lines: Jurkat, CEM, and H9. This analysis shows important mechanistic differences in integrin regulation. First, phorbol ester treatment results in increased beta 1 integrin-dependent adhesion of both Jurkat and CEM cells to fibronectin, but decreased adhesion of H9 cells. Second, certain activation stimuli that upregulate beta 1 integrin activity in peripheral T cells are nonfunctional in these T-cell lines. Third, analysis of a panel of Jurkat mutants lacking surface expression of CD2 and/or CD3 shows that CD2-mediated upregulation of beta 1 integrin activity is dependent on expression of CD3, whereas CD28-mediated upregulation is not dependent on either CD2 or CD3 expression. Fourth, all T-cell lines tested show an inability to adhere to purified ICAM-1 via LFA-1. The selective alterations in integrin regulation in these cell lines relative to peripheral blood T cells provide important insights into the intracellular processes involved in integrin activation.
Mobley
J L
JL
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor 48109-0620.
Ennis
E
E
Shimizu
Y
Y
D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D018801:CD2 Antigens; D002448:Cell Adhesion; D002460:Cell Line; D002999:Clone Cells; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D016023:Integrins / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D015458:Leukemia, T-Cell; D011971:Receptors, Immunologic / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D005353:Fibronectins; D016023:Integrins; D011971:Receptors, Immunologic