T cell receptor biases and clonal proliferations among lung transplant recipients with obliterative bronchiolitis

Steven R. Duncan, Vincent Valentine, Mihovil Roglic, Darlene J. Elias, Katherine W. Pekny, James Theodore, Dwight H. Kono, Argyrios N. Theofilopoulos

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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 β-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.

Original languageEnglish (US)
Pages (from-to)2642-2650
Number of pages9
JournalJournal of Clinical Investigation
Volume97
Issue number11
StatePublished - Jun 1 1996
Externally publishedYes

Fingerprint

Bronchiolitis
T-Cell Antigen Receptor
Lung
Allografts
Isoantigens
Lung Transplantation
Ribonucleases
Immunotherapy
Reference Values
Transplant Recipients
T-Lymphocytes
Phenotype
Polymerase Chain Reaction
Population
Genes

Keywords

  • allograft rejection, chronic
  • organ transplantation
  • T cell antigen receptors, αβ

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Duncan, S. R., Valentine, V., Roglic, M., Elias, D. J., Pekny, K. W., Theodore, J., ... Theofilopoulos, A. N. (1996). T cell receptor biases and clonal proliferations among lung transplant recipients with obliterative bronchiolitis. Journal of Clinical Investigation, 97(11), 2642-2650.

T cell receptor biases and clonal proliferations among lung transplant recipients with obliterative bronchiolitis. / Duncan, Steven R.; Valentine, Vincent; Roglic, Mihovil; Elias, Darlene J.; Pekny, Katherine W.; Theodore, James; Kono, Dwight H.; Theofilopoulos, Argyrios N.

In: Journal of Clinical Investigation, Vol. 97, No. 11, 01.06.1996, p. 2642-2650.

Research output: Contribution to journalArticle

Duncan, SR, Valentine, V, Roglic, M, Elias, DJ, Pekny, KW, Theodore, J, Kono, DH & Theofilopoulos, AN 1996, 'T cell receptor biases and clonal proliferations among lung transplant recipients with obliterative bronchiolitis', Journal of Clinical Investigation, vol. 97, no. 11, pp. 2642-2650.
Duncan SR, Valentine V, Roglic M, Elias DJ, Pekny KW, Theodore J et al. T cell receptor biases and clonal proliferations among lung transplant recipients with obliterative bronchiolitis. Journal of Clinical Investigation. 1996 Jun 1;97(11):2642-2650.
Duncan, Steven R. ; Valentine, Vincent ; Roglic, Mihovil ; Elias, Darlene J. ; Pekny, Katherine W. ; Theodore, James ; Kono, Dwight H. ; Theofilopoulos, Argyrios N. / T cell receptor biases and clonal proliferations among lung transplant recipients with obliterative bronchiolitis. In: Journal of Clinical Investigation. 1996 ; Vol. 97, No. 11. pp. 2642-2650.
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