Crosslinking of the T cell-specific accessory molecules CD7 and CD28 modulates T cell adhesion.
Regulated adhesion enables T cells to migrate through tissue and transiently interact with an endless succession of cells. Monoclonal antibody (mAb) engagement of the CD3/T cell receptor (TCR) complex results in a rapid and transient augmentation of the adhesion function of LFA-1 and VLA integrin molecules on human T cells. We show in this study that mAb crosslinking of the T cell-specific accessory molecules CD7 and CD28, or treatment with the Ca2+ ionophore A23187, results in the rapid induction of integrin-mediated adhesion to three distinct ligands: the extracellular matrix protein fibronectin, and the cell surface molecules ICAM-1 and VCAM-1. Like CD3 crosslinking, increased adhesion via CD7 and CD28 crosslinking appears to involve both protein kinase C (PKC) and cAMP-dependent protein kinases. In contrast, A23187 induction of adhesion is unaffected by PKC inhibitors. CD7 is preferentially expressed on naive T cells and is unique in being a potent inducer of naive T cell adhesion. Enhanced expression/function of adhesion-inducing molecules thus overcomes relative deficits in adhesion receptor expression.
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor 48109.
Y
Y
Shimizu
G A
GA
van Seventer
E
E
Ennis
W
W
Newman
K J
KJ
Horgan
S
S
Shaw
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D019011:Antigens, CD7; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D018106:CD28 Antigens; D017252:CD3 Complex; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D000001:Calcimycin / Q000494:pharmacology; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D016023:Integrins / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D019011:Antigens, CD7; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D016023:Integrins; D011948:Receptors, Antigen, T-Cell; D016028:Receptors, Leukocyte-Adhesion; D000001:Calcimycin