Induction of homotypic T cell adhesion by triggering of leukocyte function-associated antigen-1 alpha (CD11a): differential effects on resting and activated T cells.
The leukocyte integrin LFA-1 (CD11a/CD18) plays a key role in many adhesive interactions involving cells of the immune system. Recently, it has been shown that LFA-1 is not only involved in cell adhesion, but that stimulation of LFA-1 can also contribute to cell activation. We now demonstrate that triggering of LFA-1 on T lymphocytes by monoclonal antibodies (mAb) against the LFA-1 alpha chain, but not against the LFA-1 beta chain, promotes cell adhesion. Induction of homotypic adhesion was only observed in T cells that had been pre-activated with anti-CD3 and not in resting peripheral blood T lymphocytes. The induced homotypic adhesion is mediated by LFA-itself, because it was inhibited by anti-LFA-1 beta mAb. This notion is supported by the temperature and divalent cation dependence which is characteristic of LFA-1-mediated adhesion. mAb against ICAM-1 (CD54) did not block LFA-1 alpha-induced adhesion. The sensitivity of LFA-1 alpha-induced adhesion to H7, which prevents the activation of protein kinase C and protein kinase A, and to cytochalasin B, which inhibits microfilament formation, suggests that the activation of the LFA-1 pathway through the LFA-1 alpha chain involves cell activation and requires an intact cytoskeleton.
Department of Pathology, University of Amsterdam, The Netherlands.
G
G
Koopman
M
M
de Graaff
A C
AC
Huysmans
C J
CJ
Meijer
S T
ST
Pals
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000032:analysis; D002460:Cell Line; D003599:Cytoskeleton / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; C065289:ICAM2 protein, human; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1