Triggering of the CD44 antigen on T lymphocytes promotes T cell adhesion through the LFA-1 pathway.
The CD44 molecule, a molecule which has been previously known as Hermes, Pgp-1, extracellular matrix receptor III, and In(Lu)-related p80, is currently thought to be involved in several steps of normal immune cell function, including lymphocyte adhesion to high endothelial venules and to the extracellular matrix and T cell activation. We now demonstrate that triggering of CD44 on T lymphocytes by anti-CD44 mAb promotes cell adhesion. The induced homotypic adhesion is mediated by lymphocyte function-associated antigen-1 (LFA-1), because it was inhibited by anti-LFA-1 antibodies and not by anti-LFA-3 antibodies. This notion is supported by the temperature and Mg2+ dependence which is characteristic of LFA-1-mediated adhesion. Moreover, the sensitivity of CD44-induced adhesion to AMG and H7, which both prevent the activation of protein kinase C, and to cytochalasin B, which inhibits microfilament formation, suggests that the activation of the LFA-1 pathway via CD44 involves protein kinase C activation and requires an intact cytoskeleton.
Koopman
G
G
Department of Pathology, Free University, Amsterdam, The Netherlands.
van Kooyk
Y
Y
de Graaff
M
M
Meyer
C J
CJ
Figdor
C G
CG
Pals
S T
ST
D000911:Antibodies, Monoclonal / Q000276:immunology; D002448:Cell Adhesion; D002449:Cell Aggregation; D003599:Cytoskeleton / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D008274:Magnesium / Q000494:pharmacology; D016201:Receptors, Lymphocyte Homing / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D016169:Lymphocyte Function-Associated Antigen-1; D016201:Receptors, Lymphocyte Homing; D008274:Magnesium