Lung T-helper cells expressing T-cell receptor AV2S3 associate with clinical features of pulmonary sarcoidosis.

Abstract

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 x 10(-6)) 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.