Upregulated expression and function of VLA-4 fibronectin receptors on human activated T cells in rheumatoid arthritis.
The VLA-4 (CD49d/CD29) integrin is a cell surface receptor involved in the interaction of lymphoid cells with both extracellular matrix (ECM) and endothelial cells. We have investigated the expression and function of VLA-4 fibronectin (FN) receptors on T cells localized in the inflammed synovium of patients with rheumatoid arthritis (RA). A high proportion of T cells in both synovial membrane (SM) and synovial fluid (SF) expressed the activation antigens AIM (CD69) and gp95/85 (Ea2) as well as an increased number of VLA-4 alpha and beta 1 adhesion molecules, as compared with peripheral blood (PB) T cells from the same patients. Furthermore, the majority of these activated SF T cells were able to adhere to a 38-kD FN proteolytic fragment containing the connecting segment-1 (CS-1) specifically through VLA-4 receptors, whereas a significantly lower proportion of PB T cells displayed this capacity. Therefore, our results show that activated T cells selectively localize at sites of tissue injury in RA disease and provide evidence for the in vivo regulation of the expression and function of the VLA-4 integrin. This regulatory mechanism may enable T cells either to facilitate migration or to persist at sites of inflammation.
Laffón
A
A
Seccione de Reumatología, Hospital de la Princesa, Universidad Autónoma de Madrid, Spain.
García-Vicuña
R
R
Humbría
A
A
Postigo
A A
AA
Corbí
A L
AL
de Landázuri
M O
MO
Sánchez-Madrid
F
F
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D002448:Cell Adhesion; D005260:Female; D006649:Histocompatibility Antigens / Q000032:analysis; D006801:Humans; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D016029:Receptors, Very Late Antigen / Q000096:biosynthesis* / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D006649:Histocompatibility Antigens; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens; D016029:Receptors, Very Late Antigen; D000099192:CD69 Antigens