Obliterative bronchiolitis (OB) is the most serious late complication of lung transplantation, but the pathogenesis of this disorder has not been elucidated. We sought evidence that OB is mediated by a cellular immunologic response by characterizing T cell antigen receptor beta-chain variable gene (TCRBV) repertoires in lung allograft recipients. Expression levels of 27 TCRBV among recipients were determined by multiprobe RNase protection assay after PCR amplification. In comparison to recipients with no evidence of rejection (n = 9), the PBL TCRBV repertoires of OB subjects (n = 16) exhibited more frequent expansions (16 vs. 9% of all measured TCRBV, P < 0.02), and the magnitudes of these abnormalities were greater (8.2 +/- 0.8 vs. 4.5 +/- 0.3 SD from mean normal values, P < 0.01). TCRBV sequencing showed these expansions were composed of clonal or oligoclonal populations. Thus, T cell responses in the recipients are marked by highly selective clonal expansions, presumably driven by indirect recognition of a limited number of immunodominant alloantigens. These processes are exaggerated among allograft recipients with OB, implying that cognate immune mechanisms are important in the pathogenesis of the disorder. Furthermore, the prominence of finite, distinct TCR phenotypes raise possibilities for development of novel diagnostic modalities and targeted immunotherapies for OB and other manifestations of chronic allograft rejection.
S R Duncan, V Valentine, M Roglic, D J Elias, K W Pekny, J Theodore, D H Kono, A N Theofilopoulos
Usage data is cumulative from April 2023 through April 2024.
Usage | JCI | PMC |
---|---|---|
Text version | 90 | 8 |
37 | 9 | |
Citation downloads | 18 | 0 |
Totals | 145 | 17 |
Total Views | 162 |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.