Restricted T-cell antigen receptor repertoire in bronchoalveolar T cells from normal humans

The repertoire of variable alpha (AV) and beta (BV) TCR genes was compared in the peripheral blood and BAL fluid of five healthy individuals. Rearranged TCR transcripts were amplified by a reverse transcription-polymerase chain reaction, using oligonucleotide primers specific for 22 AV and 24 BV gene families. Nearly all AV and BV gene families were expressed in BAL T cells at levels similar to those in blood T cells. The diversity of AV and BV gene repertoire was examined further, testing the distribution of nucleotide lengths of TCR junctional regions. Most V gene families had a normal distribution of junctional region lengths in both blood and BAL T cells. Some gene families, particularly AV21 and BV9 in BAL samples, had a skewed banding pattern, with fewer bands or predominance of several bands. The limited diversity in TCR junctional region lengths was more prominent in CD8+ T cells from BAL fluids than from blood. CD4+ T cells also contributed to the limited diversity in BAL T cells. The oligoclonal expansion of bronchoalveolar CD8+ T cells was confirmed by sequence analysis of AV21-constant alpha (AC) and BV9-BC junctional regions in the blood and BAL cells. The levels of V gene expression and the diversity of junctional region lengths were very similar in T cells obtained from three separate lobes of one donor. In general, skewed patterns of TCR junctional region lengths were not consistent over time two donors, over periods of 3 and 17 months. Together, these data show that the T-cell repertoire is diverse within the lungs of normal humans, except for an oligoclonal predominance of a few V gene families in both CD4+ and CD8+ T cells. The T-cell repertoire in the lungs changes over time, which may reflect environmental exposures.