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.

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