Upregulated Expression and Function of VLA-4 Fibronectin Receptors on Human Activated T Cells in Rheumatoid Arthritis

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1991 Aug 1

PMID 1830891

Citations 57

Authors

A Laffon

R Garcia-Vicuna

A Humbria

A A Postigo

A L Corbi

M O de Landazuri

F Sanchez-Madrid

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

T cells in cardiac health and disease.

Martin P, Sanchez-Madrid F J Clin Invest. 2025; 135(2.

PMID: 39817455 PMC: 11735099. DOI: 10.1172/JCI185218.

Research progress on Th17 and T regulatory cells and their cytokines in regulating atherosclerosis.

Wang Q, Wang Y, Xu D Front Cardiovasc Med. 2022; 9:929078.

PMID: 36211578 PMC: 9534355. DOI: 10.3389/fcvm.2022.929078.

Leveraging whole blood based functional flow cytometry assays to open new perspectives for rheumatoid arthritis translational research.

Cartagena Garcia C, Balandraud N, Roudier J, Lafforgue P, Lambert N, Busnel J Sci Rep. 2022; 12(1):12166.

PMID: 35842449 PMC: 9288473. DOI: 10.1038/s41598-022-16622-4.

SPP1 promotes radiation resistance through JAK2/STAT3 pathway in esophageal carcinoma.

Wang M, Sun X, Xin H, Wen Z, Cheng Y Cancer Med. 2022; 11(23):4526-4543.

PMID: 35593388 PMC: 9741975. DOI: 10.1002/cam4.4840.

The tellurium-based immunomodulator, AS101 ameliorates adjuvant-induced arthritis in rats.

Halpert G, Halperin Sheinfeld M, Monteran L, Sharif K, Volkov A, Nadler R Clin Exp Immunol. 2020; 203(3):375-384.

PMID: 33205391 PMC: 7874835. DOI: 10.1111/cei.13553.

References

Carsons S, Mosesson M, Diamond H . Detection and quantitation of fibronectin in synovial fluid from patients with rheumatic disease. Arthritis Rheum. 1981; 24(10):1261-7. View

Scott D, Wainwright A, Walton K, Williamson N . Significance of fibronectin in rheumatoid arthritis and osteoarthrosis. Ann Rheum Dis. 1981; 40(2):142-53. PMC: 1000696. DOI: 10.1136/ard.40.2.142. View

Ishikawa H, ZIFF M . Electron microscopic observations of immunoreactive cells in the rheumatoid synovial membrane. Arthritis Rheum. 1976; 19(1):1-14. DOI: 10.1002/art.1780190101. View

Arnett F, Edworthy S, Bloch D, McShane D, Fries J, Cooper N . The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988; 31(3):315-24. DOI: 10.1002/art.1780310302. View

Dustin M, Springer T . T-cell receptor cross-linking transiently stimulates adhesiveness through LFA-1. Nature. 1989; 341(6243):619-24. DOI: 10.1038/341619a0. View

Hemler M . Adhesive protein receptors on hematopoietic cells. Immunol Today. 1988; 9(4):109-13. DOI: 10.1016/0167-5699(88)91280-7. View

Phillips D, Charo I, Parise L, Fitzgerald L . The platelet membrane glycoprotein IIb-IIIa complex. Blood. 1988; 71(4):831-43. View

Altieri D, Edgington T . The saturable high affinity association of factor X to ADP-stimulated monocytes defines a novel function of the Mac-1 receptor. J Biol Chem. 1988; 263(15):7007-15. View

Hemler M, Glass D, Coblyn J, Jacobson J . Very late activation antigens on rheumatoid synovial fluid T lymphocytes. Association with stages of T cell activation. J Clin Invest. 1986; 78(3):696-702. PMC: 423654. DOI: 10.1172/JCI112629. View

10.

Hynes R . Integrins: a family of cell surface receptors. Cell. 1987; 48(4):549-54. DOI: 10.1016/0092-8674(87)90233-9. View

11.

Akbar A, Terry L, Timms A, Beverley P, Janossy G . Loss of CD45R and gain of UCHL1 reactivity is a feature of primed T cells. J Immunol. 1988; 140(7):2171-8. View

12.

Keizer G, Borst J, Figdor C, Spits H, Miedema F, Terhorst C . Biochemical and functional characteristics of the human leukocyte membrane antigen family LFA-1, Mo-1 and p150,95. Eur J Immunol. 1985; 15(11):1142-8. DOI: 10.1002/eji.1830151114. View

13.

Detmers P, Wright S, Olsen E, Kimball B, COHN Z . Aggregation of complement receptors on human neutrophils in the absence of ligand. J Cell Biol. 1987; 105(3):1137-45. PMC: 2114803. DOI: 10.1083/jcb.105.3.1137. View

14.

Pitzalis C, Kingsley G, Murphy J, Panayi G . Abnormal distribution of the helper-inducer and suppressor-inducer T-lymphocyte subsets in the rheumatoid joint. Clin Immunol Immunopathol. 1987; 45(2):252-8. DOI: 10.1016/0090-1229(87)90040-7. View

15.

Cavender D, Haskard D, Yu C, Iguchi T, Miossec P, ZIFF M . Pathways to chronic inflammation in rheumatoid synovitis. Fed Proc. 1987; 46(1):113-7. View

16.

Ginsberg M, Loftus J, Plow E . Cytoadhesins, integrins, and platelets. Thromb Haemost. 1988; 59(1):1-6. View

17.

Wright S, Levin S, Jong M, Chad Z, Kabbash L . CR3 (CD11b/CD18) expresses one binding site for Arg-Gly-Asp-containing peptides and a second site for bacterial lipopolysaccharide. J Exp Med. 1989; 169(1):175-83. PMC: 2189200. DOI: 10.1084/jem.169.1.175. View

18.

Pitzalis C, Kingsley G, Haskard D, Panayi G . The preferential accumulation of helper-inducer T lymphocytes in inflammatory lesions: evidence for regulation by selective endothelial and homotypic adhesion. Eur J Immunol. 1988; 18(9):1397-404. DOI: 10.1002/eji.1830180915. View

19.

Pulido R, Cebrian M, Acevedo A, de Landazuri M, Sanchez-Madrid F . Comparative biochemical and tissue distribution study of four distinct CD45 antigen specificities. J Immunol. 1988; 140(11):3851-7. View

20.

Sanchez-Madrid F, de Landazuri M, Morago G, Cebrian M, Acevedo A, Bernabeu C . VLA-3: a novel polypeptide association within the VLA molecular complex: cell distribution and biochemical characterization. Eur J Immunol. 1986; 16(11):1343-9. DOI: 10.1002/eji.1830161106. View