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. 2001 Jun;56(6):487–493. doi: 10.1136/thorax.56.6.487

Intracellular cytokine repertoire in different T cell subsets from patients with sarcoidosis

M Mollers 1, S Aries 1, D Dromann 1, B Mascher 1, J Braun 1, K Dalhoff 1
PMCID: PMC1746073  PMID: 11359967

Abstract

BACKGROUND—Pulmonary sarcoidosis is characterised by a mononuclear alveolitis with a predominance of CD4+ T cells and macrophages. We determined the intracellular expression of interferon (IFN)γ, interleukin (IL)-2, tumour necrosis factor (TNF)α, IL-4, IL-5 and IL-10 in CD4+ and CD8+, naive and memory lymphocytes from blood and bronchoalveolar lavage (BAL) fluid using three colour flow cytometry.
METHODS—Eighteen untreated patients with pulmonary sarcoidosis were evaluated and stratified according to whether they had acute or chronic disease.
RESULTS—Significantly more T cells expressed Th1 than Th2 type cytokines in both BAL fluid and peripheral blood samples, regardless of clinical presentation. Significantly greater proportions of T cells secreted Th1 type cytokines in BAL fluid than in peripheral blood. Th1 type cytokines were more frequently expressed by peripheral and alveolar T cells in acute disease than in chronic disease. There were no significant differences between CD4+ and CD8+ T cells. Concerning naive and memory lymphocytes, significantly higher CD45RO:CD45RA ratios were found in BAL fluid than in blood, and increased expression of Th2 type cytokines was found in peripheral compared with alveolar memory T cells.
CONCLUSIONS—Our data support the immunopathogenetic concept of Th1/Th2 imbalance and compartmentalisation in pulmonary sarcoidosis and suggest that the cytokine patterns change during the course of disease. Expression of Th2 type cytokines in memory lymphocytes is decreased in the alveolar compartment compared with peripheral blood.



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Selected References

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

  1. Agostini C., Costabel U., Semenzato G. Sarcoidosis news: immunologic frontiers for new immunosuppressive strategies. Clin Immunol Immunopathol. 1998 Aug;88(2):199–204. doi: 10.1006/clin.1998.4544. [DOI] [PubMed] [Google Scholar]
  2. Agostini C., Trentin L., Zambello R., Bulian P., Siviero F., Masciarelli M., Festi G., Cipriani A., Semenzato G. CD8 alveolitis in sarcoidosis: incidence, phenotypic characteristics, and clinical features. Am J Med. 1993 Nov;95(5):466–472. doi: 10.1016/0002-9343(93)90328-m. [DOI] [PubMed] [Google Scholar]
  3. Allen J. E., Maizels R. M. Th1-Th2: reliable paradigm or dangerous dogma? Immunol Today. 1997 Aug;18(8):387–392. doi: 10.1016/s0167-5699(97)01102-x. [DOI] [PubMed] [Google Scholar]
  4. Atamas S. P., Yurovsky V. V., Wise R., Wigley F. M., Goter Robinson C. J., Henry P., Alms W. J., White B. Production of type 2 cytokines by CD8+ lung cells is associated with greater decline in pulmonary function in patients with systemic sclerosis. Arthritis Rheum. 1999 Jun;42(6):1168–1178. doi: 10.1002/1529-0131(199906)42:6<1168::AID-ANR13>3.0.CO;2-L. [DOI] [PubMed] [Google Scholar]
  5. Berlin M., Fogdell-Hahn A., Olerup O., Eklund A., Grunewald J. HLA-DR predicts the prognosis in Scandinavian patients with pulmonary sarcoidosis. Am J Respir Crit Care Med. 1997 Nov;156(5):1601–1605. doi: 10.1164/ajrccm.156.5.9704069. [DOI] [PubMed] [Google Scholar]
  6. Bäumer I., Zissel G., Schlaak M., Müller-Quernheim J. Th1/Th2 cell distribution in pulmonary sarcoidosis. Am J Respir Cell Mol Biol. 1997 Feb;16(2):171–177. doi: 10.1165/ajrcmb.16.2.9032124. [DOI] [PubMed] [Google Scholar]
  7. Drent M., Grutters J. C., Mulder P. G., van Velzen-Blad H., Wouters E. F., van den Bosch J. M. Is the different T helper cell activity in sarcoidosis and extrinsic allergic alveolitis also reflected by the cellular bronchoalveolar lavage fluid profile? Sarcoidosis Vasc Diffuse Lung Dis. 1997 Mar;14(1):31–38. [PubMed] [Google Scholar]
  8. Fazel S. B., Howie S. E., Krajewski A. S., Lamb D. Increased CD45RO expression on T lymphocytes in mediastinal lymph node and pulmonary lesions of patients with pulmonary sarcoidosis. Clin Exp Immunol. 1994 Mar;95(3):509–513. doi: 10.1111/j.1365-2249.1994.tb07027.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hoshino T., Itoh K., Gouhara R., Yamada A., Tanaka Y., Ichikawa Y., Azuma M., Mochizuki M., Oizumi K. Spontaneous production of various cytokines except IL-4 from CD4+ T cells in the affected organs of sarcoidosis patients. Clin Exp Immunol. 1995 Nov;102(2):399–405. doi: 10.1111/j.1365-2249.1995.tb03797.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ishioka S., Saito T., Hiyama K., Haruta Y., Maeda A., Hozawa S., Inamizu T., Yamakido M. Increased expression of tumor necrosis factor-alpha, interleukin-6, platelet-derived growth factor-B and granulocyte-macrophage colony-stimulating factor mRNA in cells of bronchoalveolar lavage fluids from patients with sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 1996 Sep;13(2):139–145. [PubMed] [Google Scholar]
  11. Jung T., Schauer U., Heusser C., Neumann C., Rieger C. Detection of intracellular cytokines by flow cytometry. J Immunol Methods. 1993 Feb 26;159(1-2):197–207. doi: 10.1016/0022-1759(93)90158-4. [DOI] [PubMed] [Google Scholar]
  12. Kunkel S. L., Lukacs N. W., Strieter R. M., Chensue S. W. Th1 and Th2 responses regulate experimental lung granuloma development. Sarcoidosis Vasc Diffuse Lung Dis. 1996 Sep;13(2):120–128. [PubMed] [Google Scholar]
  13. Mascher B., Schlenke P., Seyfarth M. Expression and kinetics of cytokines determined by intracellular staining using flow cytometry. J Immunol Methods. 1999 Feb 1;223(1):115–121. doi: 10.1016/s0022-1759(98)00200-2. [DOI] [PubMed] [Google Scholar]
  14. Minshall E. M., Tsicopoulos A., Yasruel Z., Wallaert B., Akoum H., Vorng H., Tonnel A. B., Hamid Q. Cytokine mRNA gene expression in active and nonactive pulmonary sarcoidosis. Eur Respir J. 1997 Sep;10(9):2034–2039. doi: 10.1183/09031936.97.10092034. [DOI] [PubMed] [Google Scholar]
  15. Moller D. R. Cells and cytokines involved in the pathogenesis of sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 1999 Mar;16(1):24–31. [PubMed] [Google Scholar]
  16. Moller D. R., Forman J. D., Liu M. C., Noble P. W., Greenlee B. M., Vyas P., Holden D. A., Forrester J. M., Lazarus A., Wysocka M. Enhanced expression of IL-12 associated with Th1 cytokine profiles in active pulmonary sarcoidosis. J Immunol. 1996 Jun 15;156(12):4952–4960. [PubMed] [Google Scholar]
  17. Müller-Quernheim J., Saltini C., Sondermeyer P., Crystal R. G. Compartmentalized activation of the interleukin 2 gene by lung T lymphocytes in active pulmonary sarcoidosis. J Immunol. 1986 Dec 1;137(11):3475–3483. [PubMed] [Google Scholar]
  18. Müller-Quernheim J. Sarcoidosis: immunopathogenetic concepts and their clinical application. Eur Respir J. 1998 Sep;12(3):716–738. doi: 10.1183/09031936.98.12030716. [DOI] [PubMed] [Google Scholar]
  19. Neville E., Walker A. N., James D. G. Prognostic factors predicting the outcome of sarcoidosis: an analysis of 818 patients. Q J Med. 1983 Autumn;52(208):525–533. [PubMed] [Google Scholar]
  20. Pinkston P., Bitterman P. B., Crystal R. G. Spontaneous release of interleukin-2 by lung T lymphocytes in active pulmonary sarcoidosis. N Engl J Med. 1983 Apr 7;308(14):793–800. doi: 10.1056/NEJM198304073081401. [DOI] [PubMed] [Google Scholar]
  21. Prior C., Haslam P. L. Increased levels of serum interferon-gamma in pulmonary sarcoidosis and relationship with response to corticosteroid therapy. Am Rev Respir Dis. 1991 Jan;143(1):53–60. doi: 10.1164/ajrccm/143.1.53. [DOI] [PubMed] [Google Scholar]
  22. Robinson B. W., McLemore T. L., Crystal R. G. Gamma interferon is spontaneously released by alveolar macrophages and lung T lymphocytes in patients with pulmonary sarcoidosis. J Clin Invest. 1985 May;75(5):1488–1495. doi: 10.1172/JCI111852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Saltini C., Kirby M., Trapnell B. C., Tamura N., Crystal R. G. Biased accumulation of T lymphocytes with "memory"-type CD45 leukocyte common antigen gene expression on the epithelial surface of the human lung. J Exp Med. 1990 Apr 1;171(4):1123–1140. doi: 10.1084/jem.171.4.1123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Trinchieri G. Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Annu Rev Immunol. 1995;13:251–276. doi: 10.1146/annurev.iy.13.040195.001343. [DOI] [PubMed] [Google Scholar]
  25. Walker C., Bauer W., Braun R. K., Menz G., Braun P., Schwarz F., Hansel T. T., Villiger B. Activated T cells and cytokines in bronchoalveolar lavages from patients with various lung diseases associated with eosinophilia. Am J Respir Crit Care Med. 1994 Oct;150(4):1038–1048. doi: 10.1164/ajrccm.150.4.7921434. [DOI] [PubMed] [Google Scholar]
  26. Wallace W. A., Howie S. E. Immunoreactive interleukin 4 and interferon-gamma expression by type II alveolar epithelial cells in interstitial lung disease. J Pathol. 1999 Mar;187(4):475–480. doi: 10.1002/(SICI)1096-9896(199903)187:4<475::AID-PATH268>3.0.CO;2-N. [DOI] [PubMed] [Google Scholar]
  27. Ward K., O'Connor C., Odlum C., Fitzgerald M. X. Prognostic value of bronchoalveolar lavage in sarcoidosis: the critical influence of disease presentation. Thorax. 1989 Jan;44(1):6–12. doi: 10.1136/thx.44.1.6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Westermann J., Bode U. Distribution of activated T cells migrating through the body: a matter of life and death. Immunol Today. 1999 Jul;20(7):302–306. doi: 10.1016/s0167-5699(99)01474-7. [DOI] [PubMed] [Google Scholar]

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