T-CELL RECEPTOR VARIABLE REGION GENE USAGE BY CD4+ AND CD8+ T-CELLS IN BRONCHOALVEOLAR LAVAGE FLUID AND PERIPHERAL-BLOOD OF SARCOIDOSIS PATIENTS

Sarcoidosis is a chronic noncaseating granulomatous disease of unknown etiology. An accumulation of CD4(+) T cells in the alveolar space of the lungs is a characteristic feature of the disease. We have in this study analyzed T-cell receptor (TCR) variable region (V) gene usage by CD4(+) and CD8(+) lung and peripheral blood T cells of 29 sarcoidosis patients and 15 control subjects. In the patient group, we found a 100% positive correlation between TCR V (alpha)2.3(+) CD4(+) lung T-cell expansions and the expression of the HLA-DR3(17),DQ2 haplotype. The remaining TCR V (alpha)/V (beta) gene products analyzed in this study-V (alpha)12, V (beta)2, V (beta)3, V (beta)5.1, V (beta)5.2/5.3, V (beta)5.3, V (beta)6.7, V (beta)8.1, and V (beta)12-were in general normally expressed by CD4(+) T cells, although some of them were used to a significantly higher or lower degree by lung T cells compared to peripheral blood T cells. We also performed repeated TCR V gene analyses on some HLA-DR3(+) patients and found an association between the ratio bronchoalveolar lavage fluid/peripheral blood V (alpha)2.3(+) CD4(+) T cells and clinical signs of disease activity. Finally, when analyzing TCR V gene usage by CD8(+) bronchoalveolar lavage fluid and peripheral blood T cells, a normal V (alpha,)2.3 usage was found in all cases, but lung-restricted T-cell expansions using other TCR V gene segment products were identified.