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. 1999 Apr;54(4):339–346. doi: 10.1136/thx.54.4.339

Phenotypic analysis of lymphocytes and monocytes/macrophages in peripheral blood and bronchoalveolar lavage fluid from patients with pulmonary sarcoidosis

J Wahlstrom 1, M Berlin 1, C Skold 1, H Wigzell 1, A Eklund 1, J Grunewald 1
PMCID: PMC1745457  PMID: 10092696

Abstract

BACKGROUND—The granulomatous inflammation in sarcoidosis is driven by the interplay between T cells and macrophages. To gain a better understanding of this process the expression by these cells of cell surface activation markers, co-stimulatory molecules, and adhesion molecules was analysed.
METHODS—CD4+ and CD8+ T lymphocytes from peripheral blood (PBL) or bronchoalveolar lavage (BAL) fluid, as well as paired peripheral blood monocytes and alveolar macrophages from 27 patients with sarcoidosis were analysed by flow cytometry.
RESULTS—CD26, CD54, CD69, CD95, and gp240 were all overexpressed in T cells from BAL fluid compared with those from PBL in both the CD4+ and CD8+ subsets, while CD57 was overexpressed only in BAL CD4+ cells. In contrast, CD28 tended to be underexpressed in the BAL T cells. Monocyte/macrophage markers included CD11a, CD11b, CD11c, CD14, CD16, CD54, CD71, CD80 and CD86 and HLA class II. CD11a expression in alveolar macrophages (and peripheral blood monocytes) was increased in patients with active disease and correlated positively with the percentage of BAL lymphocytes. Expression of CD80 in macrophages correlated with the BAL CD4/CD8 ratio.
CONCLUSIONS—Our data indicate substantial activation of both CD4+ and CD8+ lung T cells in sarcoidosis. There were also increased numbers of BAL lymphocytes whose phenotypic characteristics have earlier been associated with clonally expanded, replicatively senescent cells of the Th1 type.



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Selected References

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  1. Agostini C., Zambello R., Sancetta R., Cerutti A., Milani A., Tassinari C., Facco M., Cipriani A., Trentin L., Semenzato G. Expression of tumor necrosis factor-receptor superfamily members by lung T lymphocytes in interstitial lung disease. Am J Respir Crit Care Med. 1996 Apr;153(4 Pt 1):1359–1367. doi: 10.1164/ajrccm.153.4.8616567. [DOI] [PubMed] [Google Scholar]
  2. Ancochea J., González A., Sánchez M. J., Aspa J., López-Botet M. Expression of lymphocyte activation surface antigens in bronchoalveolar lavage and peripheral blood cells from young healthy subjects. Chest. 1993 Jul;104(1):32–37. doi: 10.1378/chest.104.1.32. [DOI] [PubMed] [Google Scholar]
  3. Batliwalla F., Monteiro J., Serrano D., Gregersen P. K. Oligoclonality of CD8+ T cells in health and disease: aging, infection, or immune regulation? Hum Immunol. 1996 Jun-Jul;48(1-2):68–76. doi: 10.1016/0198-8859(96)00077-8. [DOI] [PubMed] [Google Scholar]
  4. Berlin M., Lundahl J., Sköld C. M., Grunewald J., Eklund A. The lymphocytic alveolitis in sarcoidosis is associated with increased amounts of soluble and cell-bound adhesion molecules in bronchoalveolar lavage fluid and serum. J Intern Med. 1998 Oct;244(4):333–340. doi: 10.1046/j.1365-2796.1998.00378.x. [DOI] [PubMed] [Google Scholar]
  5. Chelen C. J., Fang Y., Freeman G. J., Secrist H., Marshall J. D., Hwang P. T., Frankel L. R., DeKruyff R. H., Umetsu D. T. Human alveolar macrophages present antigen ineffectively due to defective expression of B7 costimulatory cell surface molecules. J Clin Invest. 1995 Mar;95(3):1415–1421. doi: 10.1172/JCI117796. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Choremi-Papadopoulou H., Viglis V., Gargalianos P., Kordossis T., Iniotaki-Theodoraki A., Kosmidis J. Downregulation of CD28 surface antigen on CD4+ and CD8+ T lymphocytes during HIV-1 infection. J Acquir Immune Defic Syndr. 1994 Mar;7(3):245–253. [PubMed] [Google Scholar]
  7. Costabel U. CD4/CD8 ratios in bronchoalveolar lavage fluid: of value for diagnosing sarcoidosis? Eur Respir J. 1997 Dec;10(12):2699–2700. doi: 10.1183/09031936.97.10122699. [DOI] [PubMed] [Google Scholar]
  8. Dupuy d'Angeac A., Monier S., Jorgensen C., Gao Q., Travaglio-Encinoza A., Bologna C., Combe B., Sany J., Rème T. Increased percentage of CD3+, CD57+ lymphocytes in patients with rheumatoid arthritis. Correlation with duration of disease. Arthritis Rheum. 1993 May;36(5):608–612. doi: 10.1002/art.1780360506. [DOI] [PubMed] [Google Scholar]
  9. Effros R. B., Pawelec G. Replicative senescence of T cells: does the Hayflick Limit lead to immune exhaustion? Immunol Today. 1997 Sep;18(9):450–454. doi: 10.1016/s0167-5699(97)01079-7. [DOI] [PubMed] [Google Scholar]
  10. Eklund A., Blaschke E. Relationship between changed alveolar-capillary permeability and angiotensin converting enzyme activity in serum in sarcoidosis. Thorax. 1986 Aug;41(8):629–634. doi: 10.1136/thx.41.8.629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gerli R., Muscat C., Bertotto A., Bistoni O., Agea E., Tognellini R., Fiorucci G., Cesarotti M., Bombardieri S. CD26 surface molecule involvement in T cell activation and lymphokine synthesis in rheumatoid and other inflammatory synovitis. Clin Immunol Immunopathol. 1996 Jul;80(1):31–37. doi: 10.1006/clin.1996.0091. [DOI] [PubMed] [Google Scholar]
  12. Gessani S., Testa U., Varano B., Di Marzio P., Borghi P., Conti L., Barberi T., Tritarelli E., Martucci R., Seripa D. Enhanced production of LPS-induced cytokines during differentiation of human monocytes to macrophages. Role of LPS receptors. J Immunol. 1993 Oct 1;151(7):3758–3766. [PubMed] [Google Scholar]
  13. Grunewald J., Hultman T., Bucht A., Eklund A., Wigzell H. Restricted usage of T cell receptor V alpha/J alpha gene segments with different nucleotide but identical amino acid sequences in HLA-DR3+ sarcoidosis patients. Mol Med. 1995 Mar;1(3):287–296. [PMC free article] [PubMed] [Google Scholar]
  14. Hazzan M., Labalette M., Noel C., Lelievre G., Dessaint J. P. Recall response to cytomegalovirus in allograft recipients: mobilization of CD57+, CD28+ cells before expansion of CD57+, CD28- cells within the CD8+ T lymphocyte compartment. Transplantation. 1997 Mar 15;63(5):693–698. doi: 10.1097/00007890-199703150-00014. [DOI] [PubMed] [Google Scholar]
  15. Herry I., Bonay M., Bouchonnet F., Schuller M. P., Lecossier D., Tazi A., Lynch D. H., Hance A. J. Extensive apoptosis of lung T-lymphocytes maintained in vitro. Am J Respir Cell Mol Biol. 1996 Sep;15(3):339–347. doi: 10.1165/ajrcmb.15.3.8810637. [DOI] [PubMed] [Google Scholar]
  16. Hol B. E., Hintzen R. Q., Van Lier R. A., Alberts C., Out T. A., Jansen H. M. Soluble and cellular markers of T cell activation in patients with pulmonary sarcoidosis. Am Rev Respir Dis. 1993 Sep;148(3):643–649. doi: 10.1164/ajrccm/148.3.643. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Ina Y., Takada K., Yamamoto M., Morishita M., Miyachi A. Antigen-presenting capacity in patients with sarcoidosis. Chest. 1990 Oct;98(4):911–916. doi: 10.1378/chest.98.4.911. [DOI] [PubMed] [Google Scholar]
  19. Lecossier D., Valeyre D., Loiseau A., Cadranel J., Tazi A., Battesti J. P., Hance A. J. Antigen-induced proliferative response of lavage and blood T lymphocytes. Comparison of cells from normal subjects and patients with sarcoidosis. Am Rev Respir Dis. 1991 Oct;144(4):861–868. doi: 10.1164/ajrccm/144.4.861. [DOI] [PubMed] [Google Scholar]
  20. Lem V. M., Lipscomb M. F., Weissler J. C., Nunez G., Ball E. J., Stastny P., Toews G. B. Bronchoalveolar cells from sarcoid patients demonstrate enhanced antigen presentation. J Immunol. 1985 Sep;135(3):1766–1771. [PubMed] [Google Scholar]
  21. Lundahl J., Halldén G., Sköld C. M. Human blood monocytes, but not alveolar macrophages, reveal increased CD11b/CD18 expression and adhesion properties upon receptor-dependent activation. Eur Respir J. 1996 Jun;9(6):1188–1194. doi: 10.1183/09031936.96.09061188. [DOI] [PubMed] [Google Scholar]
  22. Lyons C. R., Ball E. J., Toews G. B., Weissler J. C., Stastny P., Lipscomb M. F. Inability of human alveolar macrophages to stimulate resting T cells correlates with decreased antigen-specific T cell-macrophage binding. J Immunol. 1986 Aug 15;137(4):1173–1180. [PubMed] [Google Scholar]
  23. Melis M., Gjomarkaj M., Pace E., Malizia G., Spatafora M. Increased expression of leukocyte function associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) by alveolar macrophages of patients with pulmonary sarcoidosis. Chest. 1991 Oct;100(4):910–916. doi: 10.1378/chest.100.4.910. [DOI] [PubMed] [Google Scholar]
  24. Morley J. K., Batliwalla F. M., Hingorani R., Gregersen P. K. Oligoclonal CD8+ T cells are preferentially expanded in the CD57+ subset. J Immunol. 1995 Jun 1;154(11):6182–6190. [PubMed] [Google Scholar]
  25. 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]
  26. Newman L. S., Rose C. S., Maier L. A. Sarcoidosis. N Engl J Med. 1997 Apr 24;336(17):1224–1234. doi: 10.1056/NEJM199704243361706. [DOI] [PubMed] [Google Scholar]
  27. Nicod L. P., Isler P. Alveolar macrophages in sarcoidosis coexpress high levels of CD86 (B7.2), CD40, and CD30L. Am J Respir Cell Mol Biol. 1997 Jul;17(1):91–96. doi: 10.1165/ajrcmb.17.1.2781. [DOI] [PubMed] [Google Scholar]
  28. Prieto J., Eklund A., Patarroyo M. Regulated expression of integrins and other adhesion molecules during differentiation of monocytes into macrophages. Cell Immunol. 1994 Jun;156(1):191–211. doi: 10.1006/cimm.1994.1164. [DOI] [PubMed] [Google Scholar]
  29. Roman L. I., Manzano L., De La Hera A., Abreu L., Rossi I., Alvarez-Mon M. Expanded CD4+CD45RO+ phenotype and defective proliferative response in T lymphocytes from patients with Crohn's disease. Gastroenterology. 1996 Apr;110(4):1008–1019. doi: 10.1053/gast.1996.v110.pm8612987. [DOI] [PubMed] [Google Scholar]
  30. Roussel E., Gingras M. C., Grimm E. A., Roth J. A. High expression of adhesion molecules/activation markers with little interleukin-2, interferon gamma, and tumor necrosis factor beta gene activation in fresh tumor-infiltrating lymphocytes from lung adenocarcinoma. Cancer Immunol Immunother. 1995 Jul;41(1):1–9. doi: 10.1007/BF01788953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sadat-Sowti B., Parrot A., Quint L., Mayaud C., Debre P., Autran B. Alveolar CD8+CD57+ lymphocytes in human immunodeficiency virus infection produce an inhibitor of cytotoxic functions. Am J Respir Crit Care Med. 1994 Apr;149(4 Pt 1):972–980. doi: 10.1164/ajrccm.149.4.7511468. [DOI] [PubMed] [Google Scholar]
  32. Saltini C., Hemler M. E., Crystal R. G. T lymphocytes compartmentalized on the epithelial surface of the lower respiratory tract express the very late activation antigen complex VLA-1. Clin Immunol Immunopathol. 1988 Feb;46(2):221–233. doi: 10.1016/0090-1229(88)90185-7. [DOI] [PubMed] [Google Scholar]
  33. Saltini C., Spurzem J. R., Lee J. J., Pinkston P., Crystal R. G. Spontaneous release of interleukin 2 by lung T lymphocytes in active pulmonary sarcoidosis is primarily from the Leu3+DR+ T cell subset. J Clin Invest. 1986 Jun;77(6):1962–1970. doi: 10.1172/JCI112525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Schaberg T., Rau M., Stephan H., Lode H. Increased number of alveolar macrophages expressing surface molecules of the CD11/CD18 family in sarcoidosis and idiopathic pulmonary fibrosis is related to the production of superoxide anions by these cells. Am Rev Respir Dis. 1993 Jun;147(6 Pt 1):1507–1513. doi: 10.1164/ajrccm/147.6_Pt_1.1507. [DOI] [PubMed] [Google Scholar]
  35. Scheel-Toellner D., Richter E., Toellner K. M., Reiling N., Wacker H. H., Flad H. D., Gerdes J. CD26 expression in leprosy and other granulomatous diseases correlates with the production of interferon-gamma. Lab Invest. 1995 Nov;73(5):685–690. [PubMed] [Google Scholar]
  36. Schmidt D., Goronzy J. J., Weyand C. M. CD4+ CD7- CD28- T cells are expanded in rheumatoid arthritis and are characterized by autoreactivity. J Clin Invest. 1996 May 1;97(9):2027–2037. doi: 10.1172/JCI118638. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Serrano D., Monteiro J., Allen S. L., Kolitz J., Schulman P., Lichtman S. M., Buchbinder A., Vinciguerra V. P., Chiorazzi N., Gregersen P. K. Clonal expansion within the CD4+CD57+ and CD8+CD57+ T cell subsets in chronic lymphocytic leukemia. J Immunol. 1997 Feb 1;158(3):1482–1489. [PubMed] [Google Scholar]
  38. Sköld C. M., Lundahl J., Halldén G., Hallgren M., Eklund A. Chronic smoke exposure alters the phenotype pattern and the metabolic response in human alveolar macrophages. Clin Exp Immunol. 1996 Oct;106(1):108–113. doi: 10.1046/j.1365-2249.1996.d01-805.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Strickland D. H., Thepen T., Kees U. R., Kraal G., Holt P. G. Regulation of T-cell function in lung tissue by pulmonary alveolar macrophages. Immunology. 1993 Oct;80(2):266–272. [PMC free article] [PubMed] [Google Scholar]
  40. Striz I., Wang Y. M., Kalaycioglu O., Costabel U. Expression of alveolar macrophage adhesion molecules in pulmonary sarcoidosis. Chest. 1992 Sep;102(3):882–886. doi: 10.1378/chest.102.3.882. [DOI] [PubMed] [Google Scholar]
  41. Stríz I., Wang Y. M., Svarcová I., Trnka L., Sorg C., Costabel U. The phenotype of alveolar macrophages and its correlation with immune cells in bronchoalveolar lavage. Eur Respir J. 1993 Oct;6(9):1287–1294. [PubMed] [Google Scholar]
  42. Stríz I., Wang Y. M., Teschler H., Sorg C., Costabel U. Phenotypic markers of alveolar macrophage maturation in pulmonary sarcoidosis. Lung. 1993;171(5):293–303. doi: 10.1007/BF03215872. [DOI] [PubMed] [Google Scholar]
  43. 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]
  44. Van Parijs L., Ibraghimov A., Abbas A. K. The roles of costimulation and Fas in T cell apoptosis and peripheral tolerance. Immunity. 1996 Mar;4(3):321–328. doi: 10.1016/s1074-7613(00)80440-9. [DOI] [PubMed] [Google Scholar]

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