Skip to main content
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1993 Jan;91(1):90–95. doi: 10.1111/j.1365-2249.1993.tb03360.x

Synovial fluid cells in juvenile arthritis: evidence of selective T cell migration to inflamed tissue.

E D Silverman 1, B Isacovics 1, D Petsche 1, R M Laxer 1
PMCID: PMC1554635  PMID: 8093436

Abstract

The perpetuation of chronic synovitis in juvenile arthritis (JA) is a complex interaction of local and systemic regulatory mechanism. We examined the cell surface phenotype of synovial fluid cells and peripheral blood lymphocytes from 15 patients with JA to better understand the mechanism of local inflammation. Synovial fluid and peripheral blood mononuclear cells were analysed for cell surface expression of CD2, CD3, CD4, CD8, CD19, CD25, CD29, CD45R and Ia using flow cytometry. We found a very low percentage of B cells with a concomitant increase of T cells in synovial fluid as compared with peripheral blood. A large percentage of the synovial fluid T cells were HLA-DR+, or activated T cells, and there was a relative decrease in CD4+ cells in synovial fluid as compared with peripheral blood. There was only a minimal increase in CD25+ synovial fluid cells. The synovial fluid CD4+ cells were mainly of the CD2high, CD29+, CD45RO phenotype. This CD4 phenotype found on synovial fluid cells from patients with JA and in particular the CD29 cell surface marker, which recognizes a common beta-chain of adhesion molecules, is associated with binding to extracellular matrix proteins and is also associated with 'primed' T cells. Our results demonstrated the presence of T cells which either selectively migrate to synovium and synovial fluid or are activated in situ in the joint.

Full text

PDF
90

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. Al-Balaghi S., Ström H., Möller E. B cell differentiation factor in synovial fluid of patients with rheumatoid arthritis. Immunol Rev. 1984 Apr;78:7–23. doi: 10.1111/j.1600-065x.1984.tb00474.x. [DOI] [PubMed] [Google Scholar]
  3. Alberola-Ila J., Places L., de la Calle O., Romero M., Yagüe J., Gallart T., Vives J., Lozano F. Stimulation through the TCR/CD3 complex up-regulates the CD2 surface expression on human T lymphocytes. J Immunol. 1991 Feb 15;146(4):1085–1092. [PubMed] [Google Scholar]
  4. Arnaout M. A. Structure and function of the leukocyte adhesion molecules CD11/CD18. Blood. 1990 Mar 1;75(5):1037–1050. [PubMed] [Google Scholar]
  5. Barron K. S., DeCunto C. L., Montalvo J. F., Orson F. M., Lewis D. E. Abnormalities of immunoregulation in juvenile rheumatoid arthritis. J Rheumatol. 1989 Jul;16(7):940–948. [PubMed] [Google Scholar]
  6. Bergroth V., Konttinen Y. T., Pelkonen P., Haapala M., Haapasaari J., Nordström D., Kunnamo I., Friman C. Synovial fluid lymphocytes in different subtypes of juvenile rheumatoid arthritis. Arthritis Rheum. 1988 Jun;31(6):780–783. doi: 10.1002/art.1780310613. [DOI] [PubMed] [Google Scholar]
  7. Brewer E. J., Jr, Bass J., Baum J., Cassidy J. T., Fink C., Jacobs J., Hanson V., Levinson J. E., Schaller J., Stillman J. S. Current proposed revision of JRA Criteria. JRA Criteria Subcommittee of the Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Section of The Arthritis Foundation. Arthritis Rheum. 1977 Mar;20(2 Suppl):195–199. [PubMed] [Google Scholar]
  8. Brown R. A., Jones K. L. The synthesis and accumulation of fibronectin by human articular cartilage. J Rheumatol. 1990 Jan;17(1):65–72. [PubMed] [Google Scholar]
  9. De Maria A. F., Malnati M. S., Poggi A., Pende D., Cottafava F., Moretta L. Clonal analysis of joint fluid T lymphocytes in patients with juvenile rheumatoid arthritis. J Rheumatol. 1990 Aug;17(8):1073–1078. [PubMed] [Google Scholar]
  10. Dobloug J. H., Førre O., Kvien T. K., Egeland T., Degré M. Natural killer (NK) cell activity of peripheral blood, synovial fluid, and synovial tissue lymphocytes from patients with rheumatoid arthritis and juvenile rheumatoid arthritis. Ann Rheum Dis. 1982 Oct;41(5):490–494. doi: 10.1136/ard.41.5.490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Hemler M. E., Huang C., Schwarz L. The VLA protein family. Characterization of five distinct cell surface heterodimers each with a common 130,000 molecular weight beta subunit. J Biol Chem. 1987 Mar 5;262(7):3300–3309. [PubMed] [Google Scholar]
  13. Hemler M. E., Jacobson J. G., Brenner M. B., Mann D., Strominger J. L. VLA-1: a T cell surface antigen which defines a novel late stage of human T cell activation. Eur J Immunol. 1985 May;15(5):502–508. doi: 10.1002/eji.1830150515. [DOI] [PubMed] [Google Scholar]
  14. Holzmann B., Weissman I. L. Peyer's patch-specific lymphocyte homing receptors consist of a VLA-4-like alpha chain associated with either of two integrin beta chains, one of which is novel. EMBO J. 1989 Jun;8(6):1735–1741. doi: 10.1002/j.1460-2075.1989.tb03566.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hughes C. C., Savage C. O., Pober J. S. Endothelial cells augment T cell interleukin 2 production by a contact-dependent mechanism involving CD2/LFA-3 interaction. J Exp Med. 1990 May 1;171(5):1453–1467. doi: 10.1084/jem.171.5.1453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jalkanen S., Steere A. C., Fox R. I., Butcher E. C. A distinct endothelial cell recognition system that controls lymphocyte traffic into inflamed synovium. Science. 1986 Aug 1;233(4763):556–558. doi: 10.1126/science.3726548. [DOI] [PubMed] [Google Scholar]
  17. Koyasu S., Lawton T., Novick D., Recny M. A., Siliciano R. F., Wallner B. P., Reinherz E. L. Role of interaction of CD2 molecules with lymphocyte function-associated antigen 3 in T-cell recognition of nominal antigen. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2603–2607. doi: 10.1073/pnas.87.7.2603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Laffón A., García-Vicuña R., Humbría A., Postigo A. A., Corbí A. L., de Landázuri M. O., Sánchez-Madrid F. Upregulated expression and function of VLA-4 fibronectin receptors on human activated T cells in rheumatoid arthritis. J Clin Invest. 1991 Aug;88(2):546–552. doi: 10.1172/JCI115338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Martini A., Ravelli A., Notarangelo L. D., Maccario R., Lanfranchi A., Rondena D., Ugazio A. G., Burgio R. Enhanced interleukin 1 and depressed interleukin 2 production in juvenile arthritis. J Rheumatol. 1986 Jun;13(3):598–603. [PubMed] [Google Scholar]
  20. Odum N., Morling N., Platz P., Hofmann B., Ryder L. P., Heilmann C., Pedersen F. K., Nielsen L. P., Friis J., Svejgaard A. Increased prevalence of late stage T cell activation antigen (VLA-1) in active juvenile chronic arthritis. Ann Rheum Dis. 1987 Nov;46(11):846–852. doi: 10.1136/ard.46.11.846. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Oen K. Defects in pokeweed mitogen (PWM) induced immunoglobulin (Ig) synthesis by lymphocytes of patients with juvenile rheumatoid arthritis. J Rheumatol. 1985 Aug;12(4):728–734. [PubMed] [Google Scholar]
  22. Rème T., Portier M., Frayssinoux F., Combe B., Miossec P., Favier F., Sany J. T cell receptor expression and activation of synovial lymphocyte subsets in patients with rheumatoid arthritis. Phenotyping of multiple synovial sites. Arthritis Rheum. 1990 Apr;33(4):485–492. doi: 10.1002/art.1780330404. [DOI] [PubMed] [Google Scholar]
  23. Sanders M. E., Makgoba M. W., Sharrow S. O., Stephany D., Springer T. A., Young H. A., Shaw S. 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):1401–1407. [PubMed] [Google Scholar]
  24. Serra H. M., Krowka J. F., Ledbetter J. A., Pilarski L. M. Loss of CD45R (Lp220) represents a post-thymic T cell differentiation event. J Immunol. 1988 Mar 1;140(5):1435–1441. [PubMed] [Google Scholar]
  25. Shaw S., Luce G. E., Quinones R., Gress R. E., Springer T. A., Sanders M. E. Two antigen-independent adhesion pathways used by human cytotoxic T-cell clones. Nature. 1986 Sep 18;323(6085):262–264. doi: 10.1038/323262a0. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Silverman E. D., Somma C., Khan M. M., Melmon K. L., Engleman E. G. Abnormal T suppressor cell function in juvenile rheumatoid arthritis. Arthritis Rheum. 1990 Feb;33(2):205–211. doi: 10.1002/art.1780330208. [DOI] [PubMed] [Google Scholar]
  28. Staatz W. D., Walsh J. J., Pexton T., Santoro S. A. The alpha 2 beta 1 integrin cell surface collagen receptor binds to the alpha 1 (I)-CB3 peptide of collagen. J Biol Chem. 1990 Mar 25;265(9):4778–4781. [PubMed] [Google Scholar]
  29. Takada Y., Strominger J. L., Hemler M. E. The very late antigen family of heterodimers is part of a superfamily of molecules involved in adhesion and embryogenesis. Proc Natl Acad Sci U S A. 1987 May;84(10):3239–3243. doi: 10.1073/pnas.84.10.3239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Thoen J., Førre O., Waalen K., Kåss E. Phenotypes of T lymphocytes from peripheral blood and synovial fluid of patients with rheumatoid arthritis and juvenile rheumatoid arthritis. Evidence in favour of normal helper and suppressor functions of T lymphocytes from patients with juvenile rheumatoid arthritis. Scand J Rheumatol. 1987;16(4):247–256. doi: 10.3109/03009748709102925. [DOI] [PubMed] [Google Scholar]
  31. Thomas M. L., Lefrançois L. Differential expression of the leucocyte-common antigen family. Immunol Today. 1988 Oct;9(10):320–326. doi: 10.1016/0167-5699(88)91326-6. [DOI] [PubMed] [Google Scholar]
  32. Tsokos G. C., Inghirami G., Pillemer S. R., Mavridis A., Magilavy D. B. Immunoregulatory aberrations in patients with polyarticular juvenile rheumatoid arthritis. Clin Immunol Immunopathol. 1988 Apr;47(1):62–74. doi: 10.1016/0090-1229(88)90145-6. [DOI] [PubMed] [Google Scholar]
  33. Tsokos G. C., Mavridis A., Inghirami G., Pillemer S. R., Emery H. M., Magilavy D. B. Cellular immunity in patients with systemic juvenile rheumatoid arthritis. Clin Immunol Immunopathol. 1987 Jan;42(1):86–92. doi: 10.1016/0090-1229(87)90175-9. [DOI] [PubMed] [Google Scholar]
  34. Wallace D. L., Beverley P. C. Phenotypic changes associated with activation of CD45RA+ and CD45RO+ T cells. Immunology. 1990 Mar;69(3):460–467. [PMC free article] [PubMed] [Google Scholar]
  35. Walle T. K., Vartio T., Helve T., Virtanen I., Kurki P. Cellular fibronectin in rheumatoid synovium and synovial fluid: a possible factor contributing to lymphocytic infiltration. Scand J Immunol. 1990 Apr;31(4):535–540. doi: 10.1111/j.1365-3083.1990.tb02802.x. [DOI] [PubMed] [Google Scholar]
  36. Yokoyama W. M., Maxfield S. R., Shevach E. M. Very early (VEA) and very late (VLA) activation antigens have distinct functions in T lymphocyte activation. Immunol Rev. 1989 Jun;109:153–176. doi: 10.1111/j.1600-065x.1989.tb00024.x. [DOI] [PubMed] [Google Scholar]

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

RESOURCES