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Peripheral Blood T Lymphocytes from Systemic Sclerosis Patients Show Both Th1 and Th2 Activation

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Abstract

Our objective was to investigate the phenotype of helper T cells in the peripheral blood of patients with systemic sclerosis (SSc). PBMC from 15 patients with SSc and 15 sex- and age-matched controls were investigated for lymphocyte subpopulations (CD3, CD4, CD8, CD19, CD16/CD56, CD3-DR); IL-2, IL-4, and IFN-γ mRNAs; and the relative cytokines in their cytoplasm. The last assay was carried out both in unstimulated and in PMA-activated PBMC. SSc patients presented a higher percentage of activated T cells, CD3+ DR+ (19.7 ± 9.9 vs 5.1 ± 2.5%; P < 0.0001); 12 of them presented IFN-γ mRNA-positive cells; and none IL-2 or IL-4 mRNAs. Under basal conditions, PBMC from six SSc patients contained IL-2, IL-4, and IFN-γ (i.e., they showed both Th1 and Th2 activation), and 1 IFN-γ only. PMA-stimulated PBMC of patients differed from those of controls only in the increased percentage of IFN-γ positive cells (52 ± 12 vs 37 ± 11%; P < 0.01). Our study demonstrates that Th1 activation occurs in the peripheral blood of SSc patients. This evidence must be faced with from both a pathogenetic and a therapeutical point of view.

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REFERENCES

  1. LeRoy EC: Systemic sclerosis (Scleroderma). In Cecil Textbook of Medicine, 20th ed., JC Bennett, F Plumm, DN Glass (eds). Philadelphia, WB Saunders, 1996, pp 1483-1488

    Google Scholar 

  2. White B: Pathogenesis: immune aspects. In systemic Sclerosis, PJ Clements, DE Furst (eds). Baltimore William and Wilkins, 1996, pp 229-250

    Google Scholar 

  3. Famularo A, Giacomelli R, Alesse E, Cifone MG, Morrone S, Boirivant M, Danese C, Perego MA, Santoni A, Tonietti G: Polyclonal B lymphocyte activation in progressive systemic sclerosis. J Clin Lab Immunol 29:59-63, 1989

    Google Scholar 

  4. Needleman BW, Wigley FM, Stair RW: Interleukin-1, interleukin-2, interleukin-4, interleukin-6, tumor necrosis factor a and interferon α levels in sera from patients with scleroderma. Arth Rheum 35:67-72, 1992

    Google Scholar 

  5. Giacomelli R, Cipriani P, Lattanzio R, Di Franco M, Locanto M, Parzanese I, Passacantando A, Ciocci A, Tonietti G: Circulating levels of soluble CD30 are increased in patients with systemic sclerosis (SSc) and correlate with serological and clinical features of the disease. Clin Exp Immunol 108:42-46, 1997

    Google Scholar 

  6. Mavilia C, Scaletti C, Romagnani P, Carossino A. M, Pignone A, Emmi L, Pupilli C, Pizzolo G, Maggi E, Romagnani S: Type 2 helper T-cell predominance and high CD30 expression in systemic sclerosis. Am J Pathol 151:1751-1758, 1997

    Google Scholar 

  7. Prior C, Haslam PL: In vivo and in vitro production of interferon gin fibrosing interstitial lung diseases. Clin Exp Immunol 88:280-287, 1992

    Google Scholar 

  8. Kantor TV, Medsger TA, Buckingham RB, Whiteside TL: Cytokine production and serum levels in systemic sclerosis. Clin Immunol Immunopathol 65:278-285, 1992

    Google Scholar 

  9. Kahaleh BM, LeRoy EC: Interleukin-2 in scleroderma: correlation of serum level with the extent of skin involvement and disease duration. Ann Intern Med 110:446-450, 1989

    Google Scholar 

  10. Molteni M, Della Bella S, Mascagni B, Bazzi S, Zulian C, Compasso S, Lessi M, Scorza R: Increased interferon g (IFN-g) levels produced in vitro by alloactivated T lymphocytes in systemic sclerosis and Raynaud's phenomenon. Clin Exp Immunol 116:164-168, 1999

    Google Scholar 

  11. Valentini G, Romano MF, Naclerio C, Bisogni R, Lamberti A, Turco MC, Venuta S: Increased expression of CD40 ligand in activated CD4+ T lymphocytes of systemic sclerosis patients. J Autoimmun 15:61-68, 2000

    Google Scholar 

  12. Masi AT, Rodnan GP, Medsger TA, Altman RD, D'Angelo WA, Fries JF, LeRoy EC, Kirsner AB, MacKenzie AH, McShane DJ, Myers AR, Sharp GC: Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arth Rheum 23:581-590, 1980

    Google Scholar 

  13. LeRoy EC, Black C, Fleischmajer R, Jablonska S, Krieg T, Medsger TA, Jr, Rowell N, Wollheim F: Scleroderma (systemic sclerosis): Classification, subsets and pathogenesis. J Rheumatol 15:202-205, 1988

    Google Scholar 

  14. Steen VD, Medsger TA, Rodnan GP: D-Penicillamine therapy in progressive systemic sclerosis (scleroderma): A retrospective analysis. Ann Intern Med 97:652-659, 1982

    Google Scholar 

  15. Valentini G, Vitale DF, Giunta A, Maione S, Gerundo G, Arnese MR, Tirri E, Pelaggi N, Giacummo A, Tirri G, Condorelli M: Diastolic abnormalities in systemic sclerosis: Evidence for associated defective cardiac functional reserve. Ann Rheum Dis 55:455-460, 1996

    Google Scholar 

  16. Rambaldi PF, Tontodonato V, Acampora R, Puntieri P, Di Martino N, Vatti M, Mansi L: A quantitative method to evaluate oesophageal transit with radionuclides: Comparison with manometry in Systemic Sclerosis. Eur J Nucl 24:1048, 1997

    Google Scholar 

  17. Rotondo A, Grassi R, Catalano O, Del Viscovo L, Vatti M, Gallo M, Bianco L, Celentano L, Brunetti A, Rivellini M: La patologia interstiziale polmonare nella sclerosi sistemica: Caratteristiche semeiologiche con la Tomografia Computerizzata con alta risoluzione e confronto con altre metodiche. Radiol Med 86:213-219, 1993

    Google Scholar 

  18. La Montagna G, Baruffo A, Maja L, Tirri E, Matrone C, Vatti M, Valentini G: Scleroderma renal crisis. Analysis of prevalence and outcome in a large Italian series. J Clin Rheumatol 3:188-193, 1997

    Google Scholar 

  19. Giunta A, Tirri E, Maione S, Cangianiello S, Mele A, De Luca A, Valentini G: Right ventricular diastolic abnormalities in systemic sclerosis. Relation to left ventricular involvement and pulmonary hypertension. Ann Rheum Dis 59:94-98, 2000

    Google Scholar 

  20. Valentini G: The assessment the patients with SSc: Activity and severity criteria. Systemic sclerosis towards the year 2000. International Congress on Scleroderma. Milano, Oct 3-5, 1997, p 62

  21. Freundlich B, Jimenez SA: Phenotype of peripheral blood lymphocytes in patients with progressive systemic sclerosis: Activated T lymphocytes and the effect of D-penicillamine therapy. Clin Exp Immunol 69:375-384, 1987

    Google Scholar 

  22. Degiannis D, Seibold JR, Czamecki M: Soluble interleukin-2 receptors in patients with systemic sclerosis. Clinical and laboratory correlations. Arth Rheum 33:375-380, 1990

    Google Scholar 

  23. Gustaffson R., Totterman T. H., Klareskog L., Hallgren R. Increase in activated T cells and reduction in suppressor inducer T cells in systemic sclerosis. Ann Rheum Dis 49:40-45, 1990

    Google Scholar 

  24. Fiocco U, Rosada M, Cozzi I, Ortolani C, De Silvestro G, Ruffatti A, Cozzi E, Gallo C, Todesco S: Early phenotypic activation of circulating helper memory T cells in scleroderma: Correlation with disease activity. Ann Rheum Dis 52:272-277, 1993

    Google Scholar 

  25. Roumm AD, Whiteside TA, Medsger TA, Jr, Rodnan GP: Lymphocytes in the skin of patients with progressive systemic sclerosis. Quantification, subtyping, and clinical correlations. Arth Rheum 27:645-653, 1984

    Google Scholar 

  26. Gruschwitz M, Sepp N, Kofler H, Wiek G: Expression of class II-MHC antigens in the dermis of patients with progressive systemic sclerosis. Immunobiol 182:234-255, 1991

    Google Scholar 

  27. Prescott RJ, Freemont PW, Jones CJ, Hoyland J, Fielding P: Sequential dermal microvascular and perivascular changes in the development of scleroderma. J Pathol 166:255-263, 1992

    Google Scholar 

  28. Famularo G, Procopio A, Giacomelli R, Danese C, Sacchetti S, Perego MA, Santoni A, Tonietti G: Soluble interleukin-2 receptor, interleukin-2 and interleukin-4 in sera and supernatants from patients with progressive systemic sclerosis. Clin Exp Immunol 81:368-372, 1990

    Google Scholar 

  29. Keystone EC, Lau C, Gladman D, Wilkinson S, Lee P, Shore A: Immunoregolatory T cell subpopulations in patients with scleroderma using monoclonal antibodies. Clin Exp Immunol 48:443, 1982

    Google Scholar 

  30. Hasegawa M, Fujimoto M, Kikuchi K, Takehara K: Elevated serum levels of interleukin 4 (IL-4), IL-10 and IL-13 in patients with systemic sclerosis. J Rheumatol 24:328-332, 1997

    Google Scholar 

  31. Sakkas LI, Tourtellotte C, Berney S, Myers AR, Platsoucas CD: Increased levels of alternatively spliced interleukin 4 (IL-4 delta2) transcripts in peripheral blood mononuclear cells from patients with systemic sclerosis. Clin Diagn Lab Immunol 6:660-664, 1999

    Google Scholar 

  32. Bolster MB, Ludwicka A, Sutherland SE, Strange C, Silver RM: Cytokine concentrations in bronchoalveolar lavage fluid of patients with systemic sclerosis. Arth Rheum 40:743-751, 1997

    Google Scholar 

  33. Andersson U, Andersson J, Lindfors A, Wagener K, Moller G, Heusser CH: Simultaneous production of interleukin 2, interleukin 4 and interferon-gamma by activated blood lymphocytes. Eur J Immunol 20:1591-1596, 1990

    Google Scholar 

  34. Valentini G, Della Rossa A, Bombardieri S, et al.: European multicentre study to define disease activity criteria for systemic sclerosis. II Identification of disease activity variables and development of preliminary activity indexes. Ann Rheum Dis 60, 2001

  35. Varner AE, Busse WW, Lemanske RF, Jr: Hypothesis: decreased use of pediatric aspirin has contributed to the increasing prevalence of chilhood asthma. Ann Allergy Asthma Immunol 81:347-351, 1998

    Google Scholar 

  36. Morgano A, Pierri I, Stagnaro R, Setti M, Puppo F, Indiveri F: Decreased lymphocyte blastogenesis, IL-2 production and NK activity following administration to healthy humans. Eur J Clin Pharmacol 39:545-550, 1990

    Google Scholar 

  37. Maggi E, Biswas P, Del Prete G, Parronchi P, Macchia D, Simonelli C, Emmi L, De Carli M, Tiri A, Ricci M: Accumulation of Th-2-like helper T cells in the conjunctiva of patients with vernal conjunctivitis J Immunol 146:1169-1174, 1991

    Google Scholar 

  38. Seibold JR, Giorno RC, Claman HN: Dermal mast cell degranulation systemic sclerosis. Arthritis Rheum 33:1702-1709, 1990

    Google Scholar 

  39. Cifone MG, Giacomelli R, Famularo G, Paolini R, Danese C, Napolitano T, Procopio A, Perego AM, Santoni A, Tonietti G: Natural killer activity and antibody-dependent cellular cytotoxicity in progressive systemic sclerosis. Clin Exp Immunol 80:360-365, 1990

    Google Scholar 

  40. Sambo P, Jannino L, Candela M, Salvi A, Donini M, Dusi S, Luchetti MM, Gabrielli A: Monocytes of patients with systemic sclerosis (scleroderma) spontaneously release in vitro increased amounts of superoxide anion. J Invest Dermatol 112:78-84, 1999

    Google Scholar 

  41. Del Prete G: The concept of type-1 and type-2 helper T cells and their cytokines in humans. Int Rev Immunol 16:427-455, 1998

    Google Scholar 

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Valentini, G., Baroni, A., Esposito, K. et al. Peripheral Blood T Lymphocytes from Systemic Sclerosis Patients Show Both Th1 and Th2 Activation. J Clin Immunol 21, 210–217 (2001). https://doi.org/10.1023/A:1011024313525

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