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Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 1993 Apr;52(4):272–277. doi: 10.1136/ard.52.4.272

Early phenotypic activation of circulating helper memory T cells in scleroderma: correlation with disease activity.

U Fiocco 1, M Rosada 1, L Cozzi 1, C Ortolani 1, G De Silvestro 1, A Ruffatti 1, E Cozzi 1, C Gallo 1, S Todesco 1
PMCID: PMC1005625  PMID: 8484693

Abstract

OBJECTIVES--The differential expression of several accessory/activation molecules (CD26, CD29, CD45RA, CD25, MLR4, HLA-DR) on peripheral blood CD4+ and CD8+ T lymphocytes in patients with scleroderma was compared with that in controls and patients with other connective systemic diseases to look for evidence of the involvement of T cells in the disease process of scleroderma. METHODS--The two colour expression of surface molecules by circulating T cells was analysed with a panel of monoclonal antibodies and flow cytometry in 17 patients with scleroderma, 10 patients with systemic lupus erythematosus, and five patients with rheumatoid arthritis, and the results compared with those for 10 normal controls. The two colour T CD4+ phenotype was further compared between patients with active and quiescent disease in these patients with scleroderma. The coexpression of surface molecules by CD4+ T cells was also analysed by three colour flow cytometry in eight patients with scleroderma. RESULTS--Patients with scleroderma showed increased CD4+CD26+ and CD4+CD25+ percentages and absolute numbers and decreased CD8+CD29+ percentages compared with controls. Moreover, a significant correlation between the higher CD4+CD26+ T cell percentage and absolute cell numbers with disease activity was observed. Most of the CD4+ peripheral blood T cells from patients with scleroderma showed the CD26+CD45RA- phenotype by three colour flow cytometry analysis. CONCLUSIONS--The distinctive pattern of early helper memory T cell activation in these patients with rapidly evolving scleroderma supports the role of a T cell mediated mechanism in the progression of scleroderma.

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Selected References

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  1. Arnett F. C., Edworthy S. M., Bloch D. A., McShane D. J., Fries J. F., Cooper N. S., Healey L. A., Kaplan S. R., Liang M. H., Luthra H. S. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988 Mar;31(3):315–324. doi: 10.1002/art.1780310302. [DOI] [PubMed] [Google Scholar]
  2. Beverley P. C. Is T-cell memory maintained by crossreactive stimulation? Immunol Today. 1990 Jun;11(6):203–205. doi: 10.1016/0167-5699(90)90083-l. [DOI] [PubMed] [Google Scholar]
  3. Black C. M. Systemic sclerosis: is there a treatment yet? Ann Rheum Dis. 1990 Sep;49(9):735–737. doi: 10.1136/ard.49.9.735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Corte G., Moretta L., Damiani G., Mingari M. C., Bargellesi A. Surface antigens specifically expressed by activated T cells in humans. Eur J Immunol. 1981 Feb;11(2):162–164. doi: 10.1002/eji.1830110220. [DOI] [PubMed] [Google Scholar]
  5. Cosulich M. E., Risso A., Canonica G. W., Bargellesi A. Functional characterization of a regulatory human T-cell subpopulation increasing during autologous MLR. Immunology. 1986 Feb;57(2):265–273. [PMC free article] [PubMed] [Google Scholar]
  6. D'Angelo A., Messa P., Fiocco U., Fabris A., Morachiello P., Senesi G., Todesco S. Functional renal involvement in normotensive patients with progressive systemic sclerosis: impaired sodium excretion during isotonic saline infusion. Arthritis Rheum. 1981 Jan;24(1):8–11. doi: 10.1002/art.1780240102. [DOI] [PubMed] [Google Scholar]
  7. Dang N. H., Hafler D. A., Schlossman S. F., Breitmeyer J. B. FcR-mediated crosslinking of Ta1 (CDw26) induces human T lymphocyte activation. Cell Immunol. 1990 Jan;125(1):42–57. doi: 10.1016/0008-8749(90)90061-u. [DOI] [PubMed] [Google Scholar]
  8. Dang N. H., Torimoto Y., Schlossman S. F., Morimoto C. Human CD4 helper T cell activation: functional involvement of two distinct collagen receptors, 1F7 and VLA integrin family. J Exp Med. 1990 Aug 1;172(2):649–652. doi: 10.1084/jem.172.2.649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Degiannis D., Seibold J. R., Czarnecki M., Raskova J., Raska K., Jr Soluble and cellular markers of immune activation in patients with systemic sclerosis. Clin Immunol Immunopathol. 1990 Aug;56(2):259–270. doi: 10.1016/0090-1229(90)90147-i. [DOI] [PubMed] [Google Scholar]
  10. Fox D. A., Hussey R. E., Fitzgerald K. A., Acuto O., Poole C., Palley L., Daley J. F., Schlossman S. F., Reinherz E. L. Ta1, a novel 105 KD human T cell activation antigen defined by a monoclonal antibody. J Immunol. 1984 Sep;133(3):1250–1256. [PubMed] [Google Scholar]
  11. Frieri M., Angadi C., Paolano A., Oster N., Blau S. P., Yang S., Mele C., Hawrylko E. Altered T cell subpopulations and lymphocytes expressing natural killer cell phenotypes in patients with progressive systemic sclerosis. J Allergy Clin Immunol. 1991 Apr;87(4):773–779. doi: 10.1016/0091-6749(91)90121-4. [DOI] [PubMed] [Google Scholar]
  12. Gustafsson R., Tötterman T. H., Klareskog L., Hällgren R. Increase in activated T cells and reduction in suppressor inducer T cells in systemic sclerosis. Ann Rheum Dis. 1990 Jan;49(1):40–45. doi: 10.1136/ard.49.1.40. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hafler D. A., Fox D. A., Benjamin D., Weiner H. L. Antigen reactive memory T cells are defined by Ta1. J Immunol. 1986 Jul 15;137(2):414–418. [PubMed] [Google Scholar]
  14. Kahaleh M. B., LeRoy E. C. Interleukin-2 in scleroderma: correlation of serum level with extent of skin involvement and disease duration. Ann Intern Med. 1989 Mar 15;110(6):446–450. doi: 10.7326/0003-4819-110-6-446. [DOI] [PubMed] [Google Scholar]
  15. Kahan A., Kahan A., Picard F., Menkès C. J., Amor B. Abnormalities of T lymphocyte subsets in systemic sclerosis demonstrated with anti-CD45RA and anti-CD29 monoclonal antibodies. Ann Rheum Dis. 1991 Jun;50(6):354–358. doi: 10.1136/ard.50.6.354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. LeRoy E. C., Black C., Fleischmajer R., Jablonska S., Krieg T., Medsger T. A., Jr, Rowell N., Wollheim F. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol. 1988 Feb;15(2):202–205. [PubMed] [Google Scholar]
  17. Majewski S., Hunzelmann N., Johnson J. P., Jung C., Mauch C., Ziegler-Heitbrock H. W., Riethmüller G., Krieg T. Expression of intercellular adhesion molecule-1 (ICAM-1) in the skin of patients with systemic scleroderma. J Invest Dermatol. 1991 Oct;97(4):667–671. doi: 10.1111/1523-1747.ep12483739. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Plana M., Viñas O., De la Calle-Martin O., Lozano F., Inglés-Esteve J., Romero M., Alberola-Ila J., Yagüe J., Vilella R., Vives J. Induction of interleukin 2 (IL 2) and interferon-gamma and enhancement of IL 2 receptor expression by a CD26 monoclonal antibody. Eur J Immunol. 1991 Apr;21(4):1085–1088. doi: 10.1002/eji.1830210436. [DOI] [PubMed] [Google Scholar]
  20. Roumm A. D., Whiteside T. L., Medsger T. A., Jr, Rodnan G. P. Lymphocytes in the skin of patients with progressive systemic sclerosis. Quantification, subtyping, and clinical correlations. Arthritis Rheum. 1984 Jun;27(6):645–653. doi: 10.1002/art.1780270607. [DOI] [PubMed] [Google Scholar]
  21. Ruffatti A., Peserico A., Glorioso S., Fiocco U., Rossi L., Gambari P., Todesco S. Anticentromere antibody in localized scleroderma. J Am Acad Dermatol. 1986 Oct;15(4 Pt 1):637–642. doi: 10.1016/s0190-9622(86)70217-x. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Sanders M. E., Makgoba M. W., Shaw S. Human naive and memory T cells: reinterpretation of helper-inducer and suppressor-inducer subsets. Immunol Today. 1988 Jul-Aug;9(7-8):195–199. doi: 10.1016/0167-5699(88)91212-1. [DOI] [PubMed] [Google Scholar]
  24. Scholz W., Mentlein R., Heymann E., Feller A. C., Ulmer A. J., Flad H. D. Interleukin 2 production by human T lymphocytes identified by antibodies to dipeptidyl peptidase IV. Cell Immunol. 1985 Jun;93(1):199–211. doi: 10.1016/0008-8749(85)90400-9. [DOI] [PubMed] [Google Scholar]
  25. Sollberg S., Peltonen J., Uitto J., Jimenez S. A. Elevated expression of beta 1 and beta 2 integrins, intercellular adhesion molecule 1, and endothelial leukocyte adhesion molecule 1 in the skin of patients with systemic sclerosis of recent onset. Arthritis Rheum. 1992 Mar;35(3):290–298. doi: 10.1002/art.1780350307. [DOI] [PubMed] [Google Scholar]
  26. Takeuchi T., Rudd C. E., Schlossman S. F., Morimoto C. Induction of suppression following autologous mixed lymphocyte reaction; role of a novel 2H4 antigen. Eur J Immunol. 1987 Jan;17(1):97–103. doi: 10.1002/eji.1830170117. [DOI] [PubMed] [Google Scholar]
  27. Tan E. M., Cohen A. S., Fries J. F., Masi A. T., McShane D. J., Rothfield N. F., Schaller J. G., Talal N., Winchester R. J. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982 Nov;25(11):1271–1277. doi: 10.1002/art.1780251101. [DOI] [PubMed] [Google Scholar]
  28. Ulmer A. J., Mattern T., Feller A. C., Heymann E., Flad H. D. CD26 antigen is a surface dipeptidyl peptidase IV (DPPIV) as characterized by monoclonal antibodies clone TII-19-4-7 and 4EL1C7. Scand J Immunol. 1990 Apr;31(4):429–435. doi: 10.1111/j.1365-3083.1990.tb02789.x. [DOI] [PubMed] [Google Scholar]
  29. Umehara H., Kumagai S., Ishida H., Suginoshita T., Maeda M., Imura H. Enhanced production of interleukin-2 in patients with progressive systemic sclerosis. Hyperactivity of CD4-positive T cells? Arthritis Rheum. 1988 Mar;31(3):401–407. doi: 10.1002/art.1780310312. [DOI] [PubMed] [Google Scholar]
  30. de Sousa M., Tilney N. L., Kupiec-Weglinski J. W. Recognition of self within self: specific lymphocyte positioning and the extracellular matrix. Immunol Today. 1991 Aug;12(8):262–266. doi: 10.1016/0167-5699(91)90123-B. [DOI] [PubMed] [Google Scholar]

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