SKEWING OF THE CD8-CELL REPERTOIRE IN THE LUNGS OF PATIENTS WITH SYSTEMIC-SCLEROSIS( T)

Pulmonary parenchymal involvement in SSc is characterized by alveoliti s and interstitial fibrosis, with an increased number of CD8+ T cells in BAL fluids. This study analyzed the diversity of the alpha beta T-c ell repertoire in peripheral blood and BAL fluids from seven SSc patie nts, looking for evidence of antigen-driven selection of T cells in th e lungs. A reverse transcriptase-polymerase chain reaction technique w as used to amplify rearranged TCR transcripts from unfractionated, CD4 +, and CD8+ T cells. Nearly all AV and BV gene families were expressed in SSC patients and most had similar levels of expression in blood an d BAL samples. Next, the diversity of TCR junctional region lengths wa s assessed, using sequencing gel electrophoresis. Many V gene families had a Gaussian distribution of their junctional region lengths. Howev er, some V gene families had an abnormal pattern of junctional lengths , with skewing away from a Gaussian distribution, including predominan ce of one or two lengths. This suggests selected expansion of T cells expressing those V genes. Alterations in TCR junctional region lengths were most prominent in bronchoalveolar CD8+ T cells, with similar pat terns of skewing in several patients and in one patient over time. Seq uence analysis of AV14 and BV17 junctional regions confirmed the oligo clonal character of expansion of bronchoalveolar CD8+ T cells.