CD44 antibody stimulates adhesion of peripheral blood T cells to keratinocytes through the leukocyte function-associated antigen-1/intercellular adhesion molecule-1 pathway.
Close contact between T lymphocytes and keratinocytes is an important feature of many inflammatory skin diseases. In vitro studies showed that stimulation of keratinocytes with interferon-gamma or tumor necrosis factor-alpha and of T cells with phorbol esters results in a leukocyte function-associated antigen (LFA)-1/intercellular adhesion molecule (ICAM)-1-mediated adhesion. The present study was performed to investigate the role of the CD44 molecule in keratinocyte/T-cell binding. The CD44 class of lymphocyte adhesion receptors is involved in lymphocyte binding to high endothelial venules and to extracellular matrix compounds and is therefore important in lymphocyte recirculation and homing. Moreover, CD44 can act as a co-stimulating signal in T-cell activation and promotes homotypic adhesion of in vitro cultured CD3-stimulated T cells. Using a cell adhesion assay a sixfold increase in T-cell/keratinocyte adhesion was found after pre-incubating the T cells with anti-CD44. This increased adhesion was found to require an intact cytoskeleton, to be energy and magnesium dependent, and could be completely inhibited by anti-LFA-1 and anti-ICAM-1. Pretreatment of T cells with hyaluronic acid, a ligand for CD44 and an extracellular matrix compound in the dermis and epidermis, did not affect T-cell/keratinocyte adhesion.
Bruynzeel
I
I
Department of Dermatology, Free University Hospital, Amsterdam, The Netherlands.
Koopman
G
G
van der Raaij
L M
LM
Pals
S T
ST
Willemze
R
R
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000502:physiology; D003599:Cytoskeleton / Q000502:physiology; D004734:Energy Metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1; D015603:Keratinocytes / Q000737:chemistry / Q000166:cytology* / Q000502:physiology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D008274:Magnesium / Q000494:pharmacology; D016201:Receptors, Lymphocyte Homing / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000502:physiology
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D016201:Receptors, Lymphocyte Homing; D018799:Intercellular Adhesion Molecule-1; D006820:Hyaluronic Acid; D008274:Magnesium