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Expression and functions of very late antigen 1 in inflammatory joint diseases

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Abstract

In the human immune system, very late antigen 1 (VLA-1), a putative collagen receptor, is expressed on the surface of T lymphocytes that have undergone mitogenic or antigenic stimulation. A new VLA-1-specific monoclonal antibody, 1B3.1, was used to probe the expression and function of VLA-1 on T lymphocytes in patients with arthritis. Synovial mononuclear cells from the joints of patients with rheumatoid arthritis or other joint diseases contained 32.9±13.8% 1B3.1-positive cells (42.8±10.4% in patients with rheumatoid arthritis and 28 ± 12.6% in non rheumatoid patients). In the peripheral blood, patients with active rheumatoid arthritis expressed VLA-1 on 11.7±6.0% of their mononuclear cells, compared to 1.9±1.5% in controls (P<0.001). Using dual fluorescence analysis, virtually all the 1B3.1-positive synovial cells were CD3+ T lymphocytes and included both CD4+ and CD8+ T cells. When 1B3.1-expressing synovial mononuclear cells orin vitro activated T lymphocytes were triggered with anti-CD3 antibodies, marked augmentation of their proliferation occurred if they were simultaneously cross-linked with mab 1B3.1. Collagen type IV, a putative ligand of VLA-1, also augmented T-cell proliferation to anti-CD3. The data suggest that the VLA-1 molecule could play an important role in the pathophysiology of arthritis by modulating T-cell activation in these diseases.

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References

  1. Hemler ME: Adhesive protein receptors on hematopoietic cells. Immunol Today 9:109–111, 1988

    Google Scholar 

  2. Hemler ME, Huang C, Schwartz L: The VLA family: Characterization of five distinct heterodimers each with a common 130,000 molecular weight subunit. J Biol Chem 262:3300–3309, 1987

    Google Scholar 

  3. Takada Y, Strominger JL, Hemler ME: The VLA family of heterodimers are members of a superfamily of molecules involved in adhesion and embryogenesis. Proc Natl. Acad Sci USA 84:3239–3243, 1987

    Google Scholar 

  4. Takada Y, Huang C, Hemler ME: Fibronectin receptor structures within the VLA family of heterodimers. Nature 326:607–609, 1987

    Google Scholar 

  5. Takada Y, Wayner EA, Carter WG, Hemler ME: Extracellular matrix receptors, ECMRII and ECMRI, for collagen and fibronectin correspond to VLA-2 and VLA-3 in the VLA family of heterodimers. J Cell Biochem 37(4):385–393, 1988

    Google Scholar 

  6. Maxfield SR, Moulder K, Koning F, Elbe A, Stingl G, Coligan JE, Shevach EM, Yokoyama WM: Murine T cells express a cell surface receptor for multiple extracellular matrix proteins. Identification and characterization with monoclonal antibodies. J Exp Med 169(6):2173–2190, 1989

    Google Scholar 

  7. Hemler ME, Jacobson JG: Cell matrix adhesion related proteins VLA-1 and VLA-2: Regulation of expression on T cells. J Immunol 138:2941–2948, 1987

    Google Scholar 

  8. Hemler ME, Sanchez Madrid F, Flotte TJ, Krensky AM, Burakoff SJ, Bham AK, Springer TA, Strominger JL: Glycoproteins of 210,000 and 130,000 MW on activated T cells: Cell distribution and antigen relation to components on resting cells and T cell lines. J. Immunol 132:3011–3018, 1983

    Google Scholar 

  9. Hemler ME, Ware CF, Strominger JL: Characterization of a novel differentiation antigen complex recognized by a monoclonal antibody (A1A5): Unique activation specific molecule forms on stimulated T cells. J Immunol 131:334–340, 1983

    Google Scholar 

  10. Hemler, Jacobson JG, Brenner MB, Strominger JL: VLA-1: A T cell surface antigen which defines a novel late stage of T cell activation. Eur J Immunol 15:502–508, 1985

    Google Scholar 

  11. Hemler ME, Glass D, Coblyn JS, Jacobson JG: Very late activation antigens on rheumatoid synovial fluid T lymphocytes: Association with stages of T cell activation. J Clin Invest 78:696–702, 1986

    Google Scholar 

  12. Saltini C, Hemler ME, Crystal RG: T lymphocytes compartmentalized on the epithelial surface of the lower respiratory tract express the very late activation antigen complex VLA-1. Clin Immunol Immunopathol 46:221–233, 1988

    Google Scholar 

  13. Kramer RH, Marks N: Identification of integrin collagen receptors on human melanoma cells. J Biol Chem 264:4684–4688, 1989

    Google Scholar 

  14. Bank I, Hemler ME, Brenner MB, Cohen D, Levy V, Belko J, Crouse C, Chess L: A novel monoclonal antibody, 1B3.1, binds to a new epitoipe of the VLA-1 molecule. Cell Immunol 122:416–423, 1989

    Google Scholar 

  15. Bank I, Chess L: Perturbation of the T4 molecule transmits a negative signal to T cells. J Exp Med 162:1294–1300, 1985

    Google Scholar 

  16. Kelley WN, Harris ED, Ruddy S, Sledge CB: Textbook of Rheumatology, 2nd ed. Philadelphia, WB Saunders, 1895

    Google Scholar 

  17. Laffon A, Sanchez Madrid F, Ortiz de Landazury M, Jimenez Cuesta A, Ariza A, Ossorio C, Sabando P: Very late activation antigen on synovial fluid T cells from patients with rheumatoid arthritis and rheumatic diseases. Arth Rheum 32(4):386–392, 1989

    Google Scholar 

  18. Harris, EC: Rheumatoid arthritis. Pathophysiology and implications for therapy. N Engl J Med 322:1277–1289, 1990

    Google Scholar 

  19. Geppert TD, Lipsky PE: Activation of T lymphocytes by immobilized monoclonal antibodies to CD3. Regulatory influences of mab to additional T cell determinants. J Clin Invest 81:1497–1505, 1988

    Google Scholar 

  20. Wacholtz MC, Patel SS, Lipsky PE: Leukocyte function associated antigen 1 is an activation molecule for human T cells. J Exp Med 170:431–438, 1989

    Google Scholar 

  21. Groux H, Huet S, Valentin H, Pham D, Bernard A: Suppressor effects and cyclic AMP accumulation by the CD29 molecule of CD4+ lymphocytes. Nature 339:152–154, 1989

    Google Scholar 

  22. Matsuyama T, Yamada A, Kay J, Yamada KM, Akiyama SK, Shlossman SF, Morimoto C: Activation of CD4 cells by fibronectin and anti CD3 antibody. A synergistic effect mediated by the VLA-5 fibronectin receptor complex. J Exp Med 170:1133–1148, 1989

    Google Scholar 

  23. Odum N, Morling N, Platz P, Hofmann B, Ryder PL, Heilman C, Pederson FK, Nielsen LP, Früs J, Svejgaard A: Increased prevalence of late stage T cell activation antigen (VLA-1) in active juvenile chronic arthritis. Ann Rheum Dis 46:846–852, 1987

    Google Scholar 

  24. Holtzmann B, McIntyre BW, Weissman IL: Identification of a murine peyers patch specific lymphocyte homing receptor as an integrin molecule with an alpha chain homologous to human VLA-4 alpha. Cell 56:37–46, 1989

    Google Scholar 

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Bank, I., Roth, D., Book, M. et al. Expression and functions of very late antigen 1 in inflammatory joint diseases. J Clin Immunol 11, 29–38 (1991). https://doi.org/10.1007/BF00918792

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