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

Keywords

  • Graft rejection
  • Lung transplantation
  • T lymphocytes

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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    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