Home LiteratureArticle Details
PMID: 1830891 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Upregulated expression and function of VLA-4 fibronectin receptors on human activated T cells in rheumatoid arthritis.

The Journal of clinical investigation ·Vol. 88 ·No. 2 ·1991-08-00 ·Pages 546-52

Laffón A, García-Vicuña R, Humbría A, Postigo AA, Corbí AL, de Landázuri MO, Sánchez-Madrid F

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.

MeSH Terms
Adult Aged Antigens, CD/analysis Antigens, Differentiation, T-Lymphocyte/analysis Arthritis, Rheumatoid/immunology Cell Adhesion Female Histocompatibility Antigens/analysis Humans Lectins, C-Type Leukocyte Common Antigens Lymphocyte Activation Male Middle Aged Receptors, Very Late Antigen/biosynthesis,physiology T-Lymphocytes/immunology,metabolism Up-Regulation
Chemicals
Antigens, CD Antigens, Differentiation, T-Lymphocyte CD69 antigen Histocompatibility Antigens Lectins, C-Type Receptors, Very Late Antigen Leukocyte Common Antigens
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Laffón A
Seccione de Reumatología, Hospital de la Princesa, Universidad Autónoma de Madrid, Spain.
García-Vicuña R
Humbría A
Postigo A A
Corbí A L
de Landázuri M O
Sánchez-Madrid F
References (48)
48 references, click to expand
  1. Detection and quantitation of fibronectin in synovial fluid from patients with rheumatic disease.
    Arthritis Rheum. 1981 Oct;24(10):1261-7 PMID: 6975631
  2. Significance of fibronectin in rheumatoid arthritis and osteoarthrosis.
    Ann Rheum Dis. 1981 Apr;40(2):142-53 PMID: 7013719
  3. Electron microscopic observations of immunoreactive cells in the rheumatoid synovial membrane.
    Arthritis Rheum. 1976 Jan-Feb;19(1):1-14 PMID: 1082748
  4. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis.
    Arthritis Rheum. 1988 Mar;31(3):315-24 PMID: 3358796
  5. T-cell receptor cross-linking transiently stimulates adhesiveness through LFA-1.
    Nature. 1989 Oct 19;341(6243):619-24 PMID: 2477710
  6. Adhesive protein receptors on hematopoietic cells.
    Immunol Today. 1988 Apr;9(4):109-13 PMID: 2855703
  7. The platelet membrane glycoprotein IIb-IIIa complex.
    Blood. 1988 Apr;71(4):831-43 PMID: 2833328
  8. 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 May 25;263(15):7007-15 PMID: 2835359
  9. Very late activation antigens on rheumatoid synovial fluid T lymphocytes. Association with stages of T cell activation.
    J Clin Invest. 1986 Sep;78(3):696-702 PMID: 3018043
  10. Integrins: a family of cell surface receptors.
    Cell. 1987 Feb 27;48(4):549-54 PMID: 3028640
  11. Loss of CD45R and gain of UCHL1 reactivity is a feature of primed T cells.
    J Immunol. 1988 Apr 1;140(7):2171-8 PMID: 2965180
  12. Biochemical and functional characteristics of the human leukocyte membrane antigen family LFA-1, Mo-1 and p150,95.
    Eur J Immunol. 1985 Nov;15(11):1142-8 PMID: 2933266
  13. Aggregation of complement receptors on human neutrophils in the absence of ligand.
    J Cell Biol. 1987 Sep;105(3):1137-45 PMID: 2958480
  14. Abnormal distribution of the helper-inducer and suppressor-inducer T-lymphocyte subsets in the rheumatoid joint.
    Clin Immunol Immunopathol. 1987 Nov;45(2):252-8 PMID: 2959423
  15. Pathways to chronic inflammation in rheumatoid synovitis.
    Fed Proc. 1987 Jan;46(1):113-7 PMID: 3100338
  16. Cytoadhesins, integrins, and platelets.
    Thromb Haemost. 1988 Feb 25;59(1):1-6 PMID: 3283991
  17. CR3 (CD11b/CD18) expresses one binding site for Arg-Gly-Asp-containing peptides and a second site for bacterial lipopolysaccharide.
    J Exp Med. 1989 Jan 1;169(1):175-83 PMID: 2462607
  18. The preferential accumulation of helper-inducer T lymphocytes in inflammatory lesions: evidence for regulation by selective endothelial and homotypic adhesion.
    Eur J Immunol. 1988 Sep;18(9):1397-404 PMID: 2458942
  19. Comparative biochemical and tissue distribution study of four distinct CD45 antigen specificities.
    J Immunol. 1988 Jun 1;140(11):3851-7 PMID: 2453558
  20. VLA-3: a novel polypeptide association within the VLA molecular complex: cell distribution and biochemical characterization.
    Eur J Immunol. 1986 Nov;16(11):1343-9 PMID: 2430809
  21. Antigen-specific cytotoxic T cell and antigen-specific proliferating T cell clones can be induced to cytolytic activity by monoclonal antibodies against T3.
    Eur J Immunol. 1985 Jan;15(1):88-91 PMID: 2578402
  22. Constitutive and stimulus-induced phosphorylation of CD11/CD18 leukocyte adhesion molecules.
    J Cell Biol. 1989 Dec;109(6 Pt 2):3435-44 PMID: 2574726
  23. Identification and characterization of the T lymphocyte adhesion receptor for an alternative cell attachment domain (CS-1) in plasma fibronectin.
    J Cell Biol. 1989 Sep;109(3):1321-30 PMID: 2527858
  24. Role of endothelium in chronic inflammation.
    Springer Semin Immunopathol. 1989;11(2):199-214 PMID: 2510332
  25. Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes.
    Cell. 1989 Dec 22;59(6):1203-11 PMID: 2688898
  26. Integrin molecules involved in lymphocyte homing to Peyer's patches.
    Immunol Rev. 1989 Apr;108:45-61 PMID: 2670742
  27. Distribution of the beta 1 subgroup of the integrins in human cells and tissues.
    J Histochem Cytochem. 1989 Mar;37(3):299-307 PMID: 2645360
  28. Expression of a gp33/27,000 MW activation inducer molecule (AIM) on human lymphoid tissues. Induction of cell proliferation on thymocytes and B lymphocytes by anti-AIM antibodies.
    Immunology. 1989 Sep;68(1):72-9 PMID: 2807372
  29. Very late activation antigen on synovial fluid T cells from patients with rheumatoid arthritis and other rheumatic diseases.
    Arthritis Rheum. 1989 Apr;32(4):386-92 PMID: 2784966
  30. The primary structure of the alpha 4 subunit of VLA-4: homology to other integrins and a possible cell-cell adhesion function.
    EMBO J. 1989 May;8(5):1361-8 PMID: 2788572
  31. Triggering of T cell proliferation through AIM, an activation inducer molecule expressed on activated human lymphocytes.
    J Exp Med. 1988 Nov 1;168(5):1621-37 PMID: 2903209
  32. Human memory T lymphocytes express increased levels of three cell adhesion molecules (LFA-3, CD2, and LFA-1) and three other molecules (UCHL1, CDw29, and Pgp-1) and have enhanced IFN-gamma production.
    J Immunol. 1988 Mar 1;140(5):1401-7 PMID: 2894392
  33. Phenotypic analysis of synovial tissue and peripheral blood lymphocytes isolated from patients with rheumatoid arthritis.
    Arthritis Rheum. 1988 Oct;31(10):1230-8 PMID: 3263133
  34. Fibronectin and immune complexes in rheumatic diseases.
    Ann Rheum Dis. 1987 Oct;46(10):734-40 PMID: 3500676
  35. Identification and characterization of two novel lymphocyte function-associated antigens, L24 and L25.
    J Immunol. 1987 Mar 1;138(5):1510-4 PMID: 3492556
  36. An alternative leukocyte homotypic adhesion mechanism, LFA-1/ICAM-1-independent, triggered through the human VLA-4 integrin.
    J Cell Biol. 1990 Jun;110(6):2157-65 PMID: 1693625
  37. VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/fibronectin binding site.
    Cell. 1990 Feb 23;60(4):577-84 PMID: 1689216
  38. Adhesion receptors of the immune system.
    Nature. 1990 Aug 2;346(6283):425-34 PMID: 1974032
  39. Structure of the integrin VLA-4 and its cell-cell and cell-matrix adhesion functions.
    Immunol Rev. 1990 Apr;114:45-65 PMID: 2142475
  40. The activation dependent adhesion of macrophages to laminin involves cytoskeletal anchoring and phosphorylation of the alpha 6 beta 1 integrin.
    J Cell Biol. 1990 Jun;110(6):2167-74 PMID: 2141029
  41. Regulated expression and binding of three VLA (beta 1) integrin receptors on T cells.
    Nature. 1990 May 17;345(6272):250-3 PMID: 2139716
  42. Human B lymphocytes define an alternative mechanism of adhesion to fibronectin. The interaction of the alpha 4 beta 1 integrin with the LHGPEILDVPST sequence of the type III connecting segment is sufficient to promote cell attachment.
    J Immunol. 1990 May 1;144(9):3361-6 PMID: 2139453
  43. Leukocyte adhesion to endothelium in inflammation.
    Cell. 1990 Jul 13;62(1):3-6 PMID: 2194672
  44. VLA proteins in the integrin family: structures, functions, and their role on leukocytes.
    Annu Rev Immunol. 1990;8:365-400 PMID: 2188667
  45. A monoclonal antibody to VLA-4 alpha-chain (CDw49d) induces homotypic lymphocyte aggregation.
    J Immunol. 1990 Feb 1;144(3):777-84 PMID: 2295817
  46. Glycoproteins of 210,000 and 130,000 m.w. on activated T cells: cell distribution and antigenic relation to components on resting cells and T cell lines.
    J Immunol. 1984 Jun;132(6):3011-8 PMID: 6327814
  47. Ia+ T cells in synovial fluid and tissues of patients with rheumatoid arthritis.
    Arthritis Rheum. 1981 Nov;24(11):1370-6 PMID: 6459096
  48. Different molecular forms of fibronectin in rheumatoid synovial fluid.
    Arthritis Rheum. 1982 Jan;25(1):25-31 PMID: 7066034
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI115338
Published
1991-08-00
Pages
546-52
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC295383
Subset
IM
External Links
PubMed source DOI: 10.1172/JCI115338 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2