Oligoclonal CD4+ T cell expansions in lung transplant recipients with obliterative bronchiolitis

Steven R. Duncan, Colm Leonard, James Theodore, Mark Lega, Reda E. Girgis, Glenn D. Rosen, Argyrios N. Theofilopoulos

Research output: Contribution to journalArticle

Abstract

Obliterative bronchiolitis (OB) is a dreaded and frequent complication of lung transplantation with a poorly understood immunopathogenesis. To further evaluate disease mechanisms, we used T cell antigen receptor (TCR) β-chain variable region RNase protection assays, after polymerase chain reaction amplification of TCR cDNA, to quantitate circulating CD4+ and CD8+ repertoires of transplant recipients with OB or no evidence of rejection (NER). All six recipients with OB had markedly abnormal CD4 expansions (2.5 ± 0.5 expansions/recipient) attributable to oligoclonal proliferations. Only two of six recipients with NER had a single, much lesser, CD4+ abnormality each (p <0.01). Moreover, one of these patients developed OB shortly thereafter, and the other NER abnormality may have predated transplantation. In contrast, CD8+ expansions were common in both recipient populations. Findings of CD4+ expansions had 100% sensitivity and 80% specificity for the presence or imminent development of OB. These data suggest proliferations of CD4+ T cells are important in OB pathogenesis, and these are most likely part of a major histocompatibility complex Class II-dependent process of indirect alloantigen presentation. These CD4+ clones are likely to have facultative helper functions for the multiple and diverse immune processes that have been implicated in OB. Furthermore, the close association of CD4+ expansions with OB raises possibilities of development of novel diagnostic and therapeutic approaches.

Original languageEnglish (US)
Pages (from-to)1439-1444
Number of pages6
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume165
Issue number10
DOIs
StatePublished - May 15 2002
Externally publishedYes

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Bronchiolitis
T-Lymphocytes
Lung
T-Cell Antigen Receptor
Isoantigens
Lung Transplantation
Transplant Recipients
Ribonucleases
Major Histocompatibility Complex
Complementary DNA
Clone Cells
Transplantation
Sensitivity and Specificity
Polymerase Chain Reaction

Keywords

  • Graft rejection
  • Lung transplantation
  • T lymphocytes

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Duncan, S. R., Leonard, C., Theodore, J., Lega, M., Girgis, R. E., Rosen, G. D., & Theofilopoulos, A. N. (2002). Oligoclonal CD4+ T cell expansions in lung transplant recipients with obliterative bronchiolitis. American Journal of Respiratory and Critical Care Medicine, 165(10), 1439-1444. https://doi.org/10.1164/rccm.2107009

Oligoclonal CD4+ T cell expansions in lung transplant recipients with obliterative bronchiolitis. / Duncan, Steven R.; Leonard, Colm; Theodore, James; Lega, Mark; Girgis, Reda E.; Rosen, Glenn D.; Theofilopoulos, Argyrios N.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 165, No. 10, 15.05.2002, p. 1439-1444.

Research output: Contribution to journalArticle

Duncan, SR, Leonard, C, Theodore, J, Lega, M, Girgis, RE, Rosen, GD & Theofilopoulos, AN 2002, 'Oligoclonal CD4+ T cell expansions in lung transplant recipients with obliterative bronchiolitis', American Journal of Respiratory and Critical Care Medicine, vol. 165, no. 10, pp. 1439-1444. https://doi.org/10.1164/rccm.2107009
Duncan, Steven R. ; Leonard, Colm ; Theodore, James ; Lega, Mark ; Girgis, Reda E. ; Rosen, Glenn D. ; Theofilopoulos, Argyrios N. / Oligoclonal CD4+ T cell expansions in lung transplant recipients with obliterative bronchiolitis. In: American Journal of Respiratory and Critical Care Medicine. 2002 ; Vol. 165, No. 10. pp. 1439-1444.
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