Abstract
We investigated surface antigens and spontaneous cytokine production of T cells from bronchoalveolar lavage fluid (BALF) and aqueous humor (AH) from pulmonary sarcoidosis patients for a better understanding of the role of T cells in granuloma formation. The levels of CD3, CD11b, and CD28 antigen expression on freshly isolated T cells in the BALF of patients were significantly lower than those in peripheral blood lymphocytes (PBL) of either sarcoidosis patients or healthy donors (HD). In contrast, the levels of CD80 (B7/B7-1) and CD86 (B70/B7-2) antigen expression were significantly higher on these T cells and alveolar macrophages in the BALF of patients. Fifty-three T cell clones (TCC) established from the BALF and AH of the three sarcoidosis patients displayed primarily either CD4+ CD11b+ CD28+ or CD4+ CD11b- CD28- phenotypes. Most (61-90%) of these TCC spontaneously produced greater amounts of IL-1 alpha, IL-10, tumour necrosis factor (TNF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) than did TCC from the PBL from sarcoidosis patients or HD (P < 0.05). Interferon-gamma (IFN-gamma), IL-6, and IL-2, but not IL-4, were also produced by 40-48% of these TCC. These results suggest that CD4+ T cells of the affected organs of sarcoidosis patients are activated and involved in the immunopathogenesis of sarcoidosis through production of various cytokines.
Full text
PDF






Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Azuma M., Ito D., Yagita H., Okumura K., Phillips J. H., Lanier L. L., Somoza C. B70 antigen is a second ligand for CTLA-4 and CD28. Nature. 1993 Nov 4;366(6450):76–79. doi: 10.1038/366076a0. [DOI] [PubMed] [Google Scholar]
- Azuma M., Phillips J. H., Lanier L. L. CD28- T lymphocytes. Antigenic and functional properties. J Immunol. 1993 Feb 15;150(4):1147–1159. [PubMed] [Google Scholar]
- Azuma M., Yssel H., Phillips J. H., Spits H., Lanier L. L. Functional expression of B7/BB1 on activated T lymphocytes. J Exp Med. 1993 Mar 1;177(3):845–850. doi: 10.1084/jem.177.3.845. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Branch D. R., Shah A., Guilbert L. J. A specific and reliable bioassay for the detection of femtomolar levels of human and murine tumor necrosis factors. J Immunol Methods. 1991 Oct 25;143(2):251–261. doi: 10.1016/0022-1759(91)90050-p. [DOI] [PubMed] [Google Scholar]
- Costabel U., Bross K. J., Rühle K. H., Löhr G. W., Matthys H. Ia-like antigens on T-cells and their subpopulations in pulmonary sarcoidosis and in hypersensitivity pneumonitis. Analysis of bronchoalveolar and blood lymphocytes. Am Rev Respir Dis. 1985 Mar;131(3):337–342. doi: 10.1164/arrd.1985.131.3.337. [DOI] [PubMed] [Google Scholar]
- Del Prete G. F., De Carli M., Mastromauro C., Biagiotti R., Macchia D., Falagiani P., Ricci M., Romagnani S. Purified protein derivative of Mycobacterium tuberculosis and excretory-secretory antigen(s) of Toxocara canis expand in vitro human T cells with stable and opposite (type 1 T helper or type 2 T helper) profile of cytokine production. J Clin Invest. 1991 Jul;88(1):346–350. doi: 10.1172/JCI115300. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fiorentino D. F., Bond M. W., Mosmann T. R. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med. 1989 Dec 1;170(6):2081–2095. doi: 10.1084/jem.170.6.2081. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Freeman G. J., Gribben J. G., Boussiotis V. A., Ng J. W., Restivo V. A., Jr, Lombard L. A., Gray G. S., Nadler L. M. Cloning of B7-2: a CTLA-4 counter-receptor that costimulates human T cell proliferation. Science. 1993 Nov 5;262(5135):909–911. doi: 10.1126/science.7694363. [DOI] [PubMed] [Google Scholar]
- Hoshino T., Yamada A., Honda J., Imai Y., Nakao M., Inoue M., Sagawa K., Yokoyama M. M., Oizumi K., Itoh K. Tissue-specific distribution and age-dependent increase of human CD11b+ T cells. J Immunol. 1993 Aug 15;151(4):2237–2246. [PubMed] [Google Scholar]
- Itoh K., Platsoucas C. D., Balch C. M. Autologous tumor-specific cytotoxic T lymphocytes in the infiltrate of human metastatic melanomas. Activation by interleukin 2 and autologous tumor cells, and involvement of the T cell receptor. J Exp Med. 1988 Oct 1;168(4):1419–1441. doi: 10.1084/jem.168.4.1419. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kharkevitch D. D., Seito D., Balch G. C., Maeda T., Balch C. M., Itoh K. Characterization of autologous tumor-specific T-helper 2 cells in tumor-infiltrating lymphocytes from a patient with metastatic melanoma. Int J Cancer. 1994 Aug 1;58(3):317–323. doi: 10.1002/ijc.2910580302. [DOI] [PubMed] [Google Scholar]
- Lindstein T., June C. H., Ledbetter J. A., Stella G., Thompson C. B. Regulation of lymphokine messenger RNA stability by a surface-mediated T cell activation pathway. Science. 1989 Apr 21;244(4902):339–343. doi: 10.1126/science.2540528. [DOI] [PubMed] [Google Scholar]
- Linsley P. S., Brady W., Grosmaire L., Aruffo A., Damle N. K., Ledbetter J. A. Binding of the B cell activation antigen B7 to CD28 costimulates T cell proliferation and interleukin 2 mRNA accumulation. J Exp Med. 1991 Mar 1;173(3):721–730. doi: 10.1084/jem.173.3.721. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Linsley P. S., Brady W., Urnes M., Grosmaire L. S., Damle N. K., Ledbetter J. A. CTLA-4 is a second receptor for the B cell activation antigen B7. J Exp Med. 1991 Sep 1;174(3):561–569. doi: 10.1084/jem.174.3.561. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mosmann T. R., Cherwinski H., Bond M. W., Giedlin M. A., Coffman R. L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986 Apr 1;136(7):2348–2357. [PubMed] [Google Scholar]
- Nakao M., Kubo K., Hara A., Hirohashi N., Futagami E., Shichijo S., Sagawa K., Itoh K. A monoclonal antibody (H227) recognizing a new epitope of 4F2 molecular complex associated with T cell activation. Cell Immunol. 1993 Nov;152(1):226–233. doi: 10.1006/cimm.1993.1282. [DOI] [PubMed] [Google Scholar]
- Orme I. M., Roberts A. D., Griffin J. P., Abrams J. S. Cytokine secretion by CD4 T lymphocytes acquired in response to Mycobacterium tuberculosis infection. J Immunol. 1993 Jul 1;151(1):518–525. [PubMed] [Google Scholar]
- Powrie F., Coffman R. L. Cytokine regulation of T-cell function: potential for therapeutic intervention. Immunol Today. 1993 Jun;14(6):270–274. doi: 10.1016/0167-5699(93)90044-L. [DOI] [PubMed] [Google Scholar]
- 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]
- Robinson D. S., Hamid Q., Ying S., Tsicopoulos A., Barkans J., Bentley A. M., Corrigan C., Durham S. R., Kay A. B. Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Engl J Med. 1992 Jan 30;326(5):298–304. doi: 10.1056/NEJM199201303260504. [DOI] [PubMed] [Google Scholar]
- Romagnani S. Lymphokine production by human T cells in disease states. Annu Rev Immunol. 1994;12:227–257. doi: 10.1146/annurev.iy.12.040194.001303. [DOI] [PubMed] [Google Scholar]
- Salgame P., Abrams J. S., Clayberger C., Goldstein H., Convit J., Modlin R. L., Bloom B. R. Differing lymphokine profiles of functional subsets of human CD4 and CD8 T cell clones. Science. 1991 Oct 11;254(5029):279–282. doi: 10.1126/science.254.5029.279. [DOI] [PubMed] [Google Scholar]
- Salmeron M. A., Morita T., Seki H., Platsoucas C. D., Itoh K. Lymphokine production by human melanoma tumor-infiltrating lymphocytes. Cancer Immunol Immunother. 1992;35(3):211–217. doi: 10.1007/BF01756190. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Wierenga E. A., Snoek M., de Groot C., Chrétien I., Bos J. D., Jansen H. M., Kapsenberg M. L. Evidence for compartmentalization of functional subsets of CD2+ T lymphocytes in atopic patients. J Immunol. 1990 Jun 15;144(12):4651–4656. [PubMed] [Google Scholar]
- Yamada A., Streuli M., Saito H., Rothstein D. M., Schlossman S. F., Morimoto C. Effect of activation of protein kinase C on CD45 isoform expression and CD45 protein tyrosine phosphatase activity in T cells. Eur J Immunol. 1990 Aug;20(8):1655–1660. doi: 10.1002/eji.1830200806. [DOI] [PubMed] [Google Scholar]
