Skip to main content
NCBI home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1992 Sep;89(3):439–445. doi: 10.1111/j.1365-2249.1992.tb06977.x

T lymphocyte adhesion to fibronectin (FN): a possible mechanism for T cell accumulation in the rheumatoid joint.

R M Rodriguez 1, C Pitzalis 1, G H Kingsley 1, E Henderson 1, M J Humphries 1, G S Panayi 1
PMCID: PMC1554473  PMID: 1387596

Abstract

The accumulation of T cells within the joint is responsible for the perpetuation of synovitis. This process is partly regulated by selective binding to endothelium. However, adhesion to extra-cellular matrix proteins, like FN, may also be important. FN binding is mediated by certain members of the VLA (beta 1 integrin) family of proteins. To investigate the role of Tc-FN interactions in synovitis the binding of synovial fluid (SF) and peripheral blood (PB) T cells to FN-coated wells, and the expression of cell surface VLA molecules on these cells by double label immunofluorescence, were studied. SF T cells bound better to FN than PB T cells. VLA alpha 4 and VLA beta 1 but not VLA alpha 5 were up-regulated on SF compared with PB T cells. Anti-VLA alpha 4, VLA beta 1 and VLA alpha 5 MoAbs inhibited the binding of SF T cells to FN. The increased binding of SF T cells to FN could have been related to activation and/or to their predominantly memory phenotype. Purified resting memory or naive T cells bound poorly to FN. In contrast, compared with SF T cells, concanavalin A-activated T cells showed a very similar level of binding to FN, comparable expression of VLA molecules and the same pattern of inhibition of binding to FN by MoAbs. Thus, VLA molecules may play an important role in the retention of T cells in the joint and since T cells can be activated via VLA-FN interactions, this mechanism may perpetuate chronic inflammation.

Full text

PDF
439

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akbar A. N., Terry L., Timms A., Beverley P. C., Janossy G. Loss of CD45R and gain of UCHL1 reactivity is a feature of primed T cells. J Immunol. 1988 Apr 1;140(7):2171–2178. [PubMed] [Google Scholar]
  2. Bergroth V., Konttinen Y. T., Nykänen P., von Essen R., Koota K. Proliferating cells in the synovial fluid in rheumatic disease. An analysis with autoradiography-immunoperoxidase double staining. Scand J Immunol. 1985 Oct;22(4):383–388. doi: 10.1111/j.1365-3083.1985.tb01896.x. [DOI] [PubMed] [Google Scholar]
  3. Bonvoisin B., Cordier G., Revillard J. P., Lejeune E., Bouvier M. Increased DNA and/or RNA content of synovial fluid cells in rheumatoid arthritis: a flow-cytometry study. Ann Rheum Dis. 1984 Apr;43(2):222–227. doi: 10.1136/ard.43.2.222. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cassiman J. J. The involvement of the cell matrix receptors, or VLA integrins, in the morphogenetic behavior of normal and malignant cells is gradually being uncovered. Cancer Genet Cytogenet. 1989 Aug;41(1):19–32. doi: 10.1016/0165-4608(89)90104-0. [DOI] [PubMed] [Google Scholar]
  5. Elices M. J., Osborn L., Takada Y., Crouse C., Luhowskyj S., Hemler M. E., Lobb R. R. 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):577–584. doi: 10.1016/0092-8674(90)90661-w. [DOI] [PubMed] [Google Scholar]
  6. Gailit J., Ruoslahti E. Regulation of the fibronectin receptor affinity by divalent cations. J Biol Chem. 1988 Sep 15;263(26):12927–12932. [PubMed] [Google Scholar]
  7. Garcia-Pardo A., Ferreira O. C. Adhesion of human T-lymphoid cells to fibronectin is mediated by two different fibronectin domains. Immunology. 1990 Jan;69(1):121–126. [PMC free article] [PubMed] [Google Scholar]
  8. Groux H., Huet S., Valentin H., Pham D., Bernard A. Suppressor effects and cyclic AMP accumulation by the CD29 molecule of CD4+ lymphocytes. Nature. 1989 May 11;339(6220):152–154. doi: 10.1038/339152a0. [DOI] [PubMed] [Google Scholar]
  9. Hemler M. E., Glass D., Coblyn J. S., Jacobson J. G. 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. doi: 10.1172/JCI112629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hemler M. E. VLA proteins in the integrin family: structures, functions, and their role on leukocytes. Annu Rev Immunol. 1990;8:365–400. doi: 10.1146/annurev.iy.08.040190.002053. [DOI] [PubMed] [Google Scholar]
  11. Holzmann B., McIntyre B. W., Weissman I. L. Identification of a murine Peyer's patch--specific lymphocyte homing receptor as an integrin molecule with an alpha chain homologous to human VLA-4 alpha. Cell. 1989 Jan 13;56(1):37–46. doi: 10.1016/0092-8674(89)90981-1. [DOI] [PubMed] [Google Scholar]
  12. Humphries M. J., Akiyama S. K., Komoriya A., Olden K., Yamada K. M. Identification of an alternatively spliced site in human plasma fibronectin that mediates cell type-specific adhesion. J Cell Biol. 1986 Dec;103(6 Pt 2):2637–2647. doi: 10.1083/jcb.103.6.2637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Humphries M. J., Komoriya A., Akiyama S. K., Olden K., Yamada K. M. Identification of two distinct regions of the type III connecting segment of human plasma fibronectin that promote cell type-specific adhesion. J Biol Chem. 1987 May 15;262(14):6886–6892. [PubMed] [Google Scholar]
  14. Humphries M. J., Obara M., Olden K., Yamada K. M. Role of fibronectin in adhesion, migration, and metastasis. Cancer Invest. 1989;7(4):373–393. doi: 10.3109/07357908909039866. [DOI] [PubMed] [Google Scholar]
  15. Humphries M. J. The molecular basis and specificity of integrin-ligand interactions. J Cell Sci. 1990 Dec;97(Pt 4):585–592. doi: 10.1242/jcs.97.4.585. [DOI] [PubMed] [Google Scholar]
  16. Kingsley G., Pitzalis C., Kyriazis N., Panayi G. S. Abnormal helper-inducer/suppressor-inducer T-cell subset distribution and T-cell activation status are common to all types of chronic synovitis. Scand J Immunol. 1988 Aug;28(2):225–232. doi: 10.1111/j.1365-3083.1988.tb02435.x. [DOI] [PubMed] [Google Scholar]
  17. Konttinen Y., Bergroth V., Nykänen P. Lymphocyte activation in rheumatoid arthritis synovial fluid in vivo. Scand J Immunol. 1985 Nov;22(5):503–507. doi: 10.1111/j.1365-3083.1985.tb01909.x. [DOI] [PubMed] [Google Scholar]
  18. Krotoski D., Bronner-Fraser M. Distribution of integrins and their ligands in the trunk of Xenopus laevis during neural crest cell migration. J Exp Zool. 1990 Feb;253(2):139–150. doi: 10.1002/jez.1402530204. [DOI] [PubMed] [Google Scholar]
  19. Kurki P., Vartio T., Virtanen I. Mitogen stimulation promotes human T lymphocyte adhesion to fibronectin. Scand J Immunol. 1987 Dec;26(6):645–652. doi: 10.1111/j.1365-3083.1987.tb02300.x. [DOI] [PubMed] [Google Scholar]
  20. Larson R. S., Springer T. A. Structure and function of leukocyte integrins. Immunol Rev. 1990 Apr;114:181–217. doi: 10.1111/j.1600-065x.1990.tb00565.x. [DOI] [PubMed] [Google Scholar]
  21. Lash J. W., Gosfield E., 3rd, Ostrovsky D., Bellairs R. Migration of chick blastoderm under the vitelline membrane: the role of fibronectin. Dev Biol. 1990 Jun;139(2):407–416. doi: 10.1016/0012-1606(90)90309-7. [DOI] [PubMed] [Google Scholar]
  22. Matsuyama T., Yamada A., Kay J., Yamada K. M., Akiyama S. K., Schlossman S. F., 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. 1989 Oct 1;170(4):1133–1148. doi: 10.1084/jem.170.4.1133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Morimoto C., Letvin N. L., Boyd A. W., Hagan M., Brown H. M., Kornacki M. M., Schlossman S. F. The isolation and characterization of the human helper inducer T cell subset. J Immunol. 1985 Jun;134(6):3762–3769. [PubMed] [Google Scholar]
  24. Mould A. P., Wheldon L. A., Komoriya A., Wayner E. A., Yamada K. M., Humphries M. J. Affinity chromatographic isolation of the melanoma adhesion receptor for the IIICS region of fibronectin and its identification as the integrin alpha 4 beta 1. J Biol Chem. 1990 Mar 5;265(7):4020–4024. [PubMed] [Google Scholar]
  25. Nojima Y., Humphries M. J., Mould A. P., Komoriya A., Yamada K. M., Schlossman S. F., Morimoto C. VLA-4 mediates CD3-dependent CD4+ T cell activation via the CS1 alternatively spliced domain of fibronectin. J Exp Med. 1990 Oct 1;172(4):1185–1192. doi: 10.1084/jem.172.4.1185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Paul J. I., Schwarzbauer J. E., Tamkun J. W., Hynes R. O. Cell-type-specific fibronectin subunits generated by alternative splicing. J Biol Chem. 1986 Sep 15;261(26):12258–12265. [PubMed] [Google Scholar]
  27. Pierschbacher M. D., Ruoslahti E. Cell attachment activity of fibronectin can be duplicated by small synthetic fragments of the molecule. Nature. 1984 May 3;309(5963):30–33. doi: 10.1038/309030a0. [DOI] [PubMed] [Google Scholar]
  28. Pierschbacher M., Hayman E. G., Ruoslahti E. Synthetic peptide with cell attachment activity of fibronectin. Proc Natl Acad Sci U S A. 1983 Mar;80(5):1224–1227. doi: 10.1073/pnas.80.5.1224. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Pitzalis C., Kingsley G. H., Covelli M., Meliconi R., Markey A., Panayi G. S. Selective migration of the human helper-inducer memory T cell subset: confirmation by in vivo cellular kinetic studies. Eur J Immunol. 1991 Feb;21(2):369–376. doi: 10.1002/eji.1830210218. [DOI] [PubMed] [Google Scholar]
  30. 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 Sep;18(9):1397–1404. doi: 10.1002/eji.1830180915. [DOI] [PubMed] [Google Scholar]
  31. 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 Nov;45(2):252–258. doi: 10.1016/0090-1229(87)90040-7. [DOI] [PubMed] [Google Scholar]
  32. Pulido R., Elices M. J., Campanero M. R., Osborn L., Schiffer S., García-Pardo A., Lobb R., Hemler M. E., Sánchez-Madrid F. Functional evidence for three distinct and independently inhibitable adhesion activities mediated by the human integrin VLA-4. Correlation with distinct alpha 4 epitopes. J Biol Chem. 1991 Jun 5;266(16):10241–10245. [PubMed] [Google Scholar]
  33. Ruoslahti E. Fibronectin and its receptors. Annu Rev Biochem. 1988;57:375–413. doi: 10.1146/annurev.bi.57.070188.002111. [DOI] [PubMed] [Google Scholar]
  34. Scott D. L., Delamere J. P., Walton K. W. The distribution of fibronectin in the pannus in rheumatoid arthritis. Br J Exp Pathol. 1981 Aug;62(4):362–368. [PMC free article] [PubMed] [Google Scholar]
  35. Shimizu Y., Van Seventer G. A., Horgan K. J., Shaw S. Regulated expression and binding of three VLA (beta 1) integrin receptors on T cells. Nature. 1990 May 17;345(6272):250–253. doi: 10.1038/345250a0. [DOI] [PubMed] [Google Scholar]
  36. Shimizu Y., van Seventer G. A., Horgan K. J., Shaw S. Costimulation of proliferative responses of resting CD4+ T cells by the interaction of VLA-4 and VLA-5 with fibronectin or VLA-6 with laminin. J Immunol. 1990 Jul 1;145(1):59–67. [PubMed] [Google Scholar]
  37. Stoolman L. M. Adhesion molecules controlling lymphocyte migration. Cell. 1989 Mar 24;56(6):907–910. doi: 10.1016/0092-8674(89)90620-x. [DOI] [PubMed] [Google Scholar]
  38. Takada Y., Huang C., Hemler M. E. Fibronectin receptor structures in the VLA family of heterodimers. Nature. 1987 Apr 9;326(6113):607–609. doi: 10.1038/326607a0. [DOI] [PubMed] [Google Scholar]
  39. Vartio T., Vaheri A., Von Essen R., Isomäki H., Stenman S. Fibronectin in synovial fluid and tissue in rheumatoid arthritis. Eur J Clin Invest. 1981 Jun;11(3):207–212. doi: 10.1111/j.1365-2362.1981.tb01842.x. [DOI] [PubMed] [Google Scholar]
  40. Wayner E. A., Garcia-Pardo A., Humphries M. J., McDonald J. A., Carter W. G. 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):1321–1330. doi: 10.1083/jcb.109.3.1321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Yamada A., Nikaido T., Nojima Y., Schlossman S. F., Morimoto C. Activation of human CD4 T lymphocytes. Interaction of fibronectin with VLA-5 receptor on CD4 cells induces the AP-1 transcription factor. J Immunol. 1991 Jan 1;146(1):53–56. [PubMed] [Google Scholar]
  42. Yednock T. A., Rosen S. D. Lymphocyte homing. Adv Immunol. 1989;44:313–378. doi: 10.1016/s0065-2776(08)60645-8. [DOI] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES