Am. J. Respir. Crit. Care Med., Volume 161, Number 3, March 2000, 814-818

Lung T-Helper Cells Expressing T-cell Receptor AV2S3 Associate with Clinical Features of Pulmonary Sarcoidosis

JOHAN GRUNEWALD, MARY BERLIN, OLLE OLERUP, and ANDERS EKLUND

Department of Medicine, Division of Respiratory Medicine, Karolinska Hospital, Stockholm; and Department of Biosciences at Novum and Division of Clinical Immunology, Huddinge Hospital, Huddinge, Sweden

In previous reports of studies of Scandinavian sarcoidosis patients, we have described a strong association between lung-restricted expansions of T cells expressing T-cell receptor (TCR) AV2S3 and the human leukocyte antigen (HLA)-DRB1*0301 (DR17) and -DRB3*0101 alleles, suggesting the presence of a specific antigen in sarcoidosis. In the present study, the degree of lung-accumulated TCR AV2S3⁺ T cells was related to clinical data in 51 HLA-DRB1*0301/DRB3*0101-positive Scandinavian patients with pulmonary sarcoidosis. Significantly more AV2S3⁺ lung T cells (median: 30.0% of CD4⁺ cells in bronchoalveolar lavage fluid [BALF]) were found accumulated in patients with a short (< 2 yr) than with a long (> 2 yr) (median: 18.6%) disease duration (p = 0.003). A strong positive association was also found between lung-restricted AV2S3⁺ T cells and both the CD4⁺-to-CD8⁺ cell ratio (p = 7 × 10⁶) in BALF and with an acute disease onset (p = 0.018). Negative associations were found between both the interval from disease onset to bronchoalveolar lavage (p = 0.0001) and the age of the patient (p = 0.002). Our findings strongly link lung-accumulated AV2S3⁺ T cells to the acute inflammatory response in sarcoidosis. Moreover, the association of these cells with a good prognosis indicates that AV2S3⁺ T cells may have a protective role against a presumed sarcoidosis antigen. Grunewald J, Berlin M, Olerup O, Eklund A. Lung T-helper cells expressing T-cell receptor AV2S3 associate with clinical features of pulmonary sarcoidosis.

This article has been cited by other articles:

				E. S. Chen, J. Wahlstrom, Z. Song, M. H. Willett, M. Wiken, R. C. Yung, E. E. West, J. F. McDyer, Y. Zhang, A. Eklund, et al. T Cell Responses to Mycobacterial Catalase-Peroxidase Profile a Pathogenic Antigen in Systemic Sarcoidosis J. Immunol., December 15, 2008; 181(12): 8784 - 8796. [Abstract] [Full Text] [PDF]

				A. C. Jonth, L. Silveira, T. E. Fingerlin, H. Sato, J. C. Luby, K. I. Welsh, C. S. Rose, L. S. Newman, R. M. du Bois, L. A. Maier, et al. TGF-beta1 Variants in Chronic Beryllium Disease and Sarcoidosis J. Immunol., September 15, 2007; 179(6): 4255 - 4262. [Abstract] [Full Text] [PDF]

				J. Grunewald and A. Eklund State of the Art. Role of CD4+ T Cells in Sarcoidosis Proceedings of the ATS, August 15, 2007; 4(5): 461 - 464. [Abstract] [Full Text] [PDF]

				O. P. Sharma Murray Kornfeld, American College of Chest Physician, and Sarcoidosis: a Historical Footnote: 2004 Murray Kornfeld Memorial Founders Lecture Chest, September 1, 2005; 128(3): 1830 - 1835. [Abstract] [Full Text] [PDF]

				N. Kaminski, J. A. Belperio, P. B. Bitterman, L. Chen, S. W. Chensue, A. M.K. Choi, S. Dacic, J. H. Dauber, R. M. du Bois, J. J. Enghild, et al. Idiopathic Pulmonary Fibrosis Am. J. Respir. Cell Mol. Biol., September 1, 2003; 29(3): S1 - 105. [Full Text] [PDF]

				A. Planck, A. Eklund, and J. Grunewald Markers of activity in clinically recovered human leukocyte antigen-DR17-positive sarcoidosis patients Eur. Respir. J., January 1, 2003; 21(1): 52 - 57. [Abstract] [Full Text] [PDF]

				D. R. Moller and E. S. Chen Genetic Basis of Remitting Sarcoidosis: Triumph of the Trimolecular Complex? Am. J. Respir. Cell Mol. Biol., October 1, 2002; 27(4): 391 - 395. [Full Text] [PDF]

				J Grunewald, J Wahlstrom, M Berlin, H Wigzell, A Eklund, and O Olerup Lung restricted T cell receptor AV2S3+ CD4+ T cell expansions in sarcoidosis patients with a shared HLA-DR{beta} chain conformation Thorax, April 1, 2002; 57(4): 348 - 352. [Abstract] [Full Text] [PDF]

				M. J. TOBIN Tuberculosis, Lung Infections, and Interstitial Lung Disease in AJRCCM 2000 Am. J. Respir. Crit. Care Med., November 15, 2001; 164(10): 1774 - 1788. [Full Text] [PDF]

				M. J. Tobin Taxonomy of AJRCCM, a New Series, and a Medley of Metaphors Am. J. Respir. Crit. Care Med., October 15, 2001; 164(8): 1333 - 1335. [Full Text] [PDF]

				M. SCHURMANN, P. REICHEL, B. MULLER-MYHSOK, M. SCHLAAK, J. MULLER-QUERNHEIM, and E. SCHWINGER Results from a Genome-wide Search for Predisposing Genes in Sarcoidosis Am. J. Respir. Crit. Care Med., September 1, 2001; 164(5): 840 - 846. [Abstract] [Full Text] [PDF]

				K. KATCHAR, J. WAHLSTROM, A. EKLUND, and J. GRUNEWALD Highly Activated T-Cell Receptor AV2S3+ CD4+ Lung T-Cell Expansions in Pulmonary Sarcoidosis Am. J. Respir. Crit. Care Med., June 1, 2001; 163(7): 1540 - 1545. [Abstract] [Full Text] [PDF]

				J. Grunewald and A. Eklund Human leukocyte antigen genes may outweigh racial background when generating a specific immune response in sarcoidosis Eur. Respir. J., May 1, 2001; 17(5): 1046 - 1048. [Abstract] [Full Text] [PDF]