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Published ahead of print on June 3, 2005, doi:10.1164/rccm.200410-1332OC

Am. J. Respir. Crit. Care Med., Volume 172, Number 5, September 2005, 590-596

A more recent version of this article appeared on September 1, 2005
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Submitted on October 7, 2004
Accepted on May 25, 2005

Oligoclonal CD4+ T Cells in the Lungs of Patients with Severe Emphysema

Andrew K Sullivan1, Philip L Simonian1, Michael T Falta1, John D Mitchell2, Gregory P Cosgrove3, Kevin K Brown3, Brian L Kotzin4, Norbert F Voelkel1, and Andrew P Fontenot4*

1 Department of Medicine, University of Colorado, Denver, CO, USA, 2 Department of Surgery, University of Colorado, Denver, CO, USA, 3 Department of Medicine, National Jewish Medical and Research Center, Denver, CO, USA, 4 Department of Medicine, University of Colorado, Denver, CO, USA; Department of Immunology, University of Colorado, Denver, CO, USA

* To whom correspondence should be addressed. E-mail: andrew.fontenot{at}uchsc.edu.

Rationale: Within the lungs of patients with severe emphysema, inflammation continues despite smoking cessation. Foci of T lymphocytes in the small airways of emphysema patients have been associated with disease severity. Whether these T cells play an important role in this continued inflammatory response is unknown. Objective: The aim of this study was to determine if T cells recruited to the lungs of severe emphysema subjects contain oligoclonal T cell populations, suggesting their accumulation in response to antigenic stimuli. Methods: Lung T cell receptor (TCR) V{beta} repertoire from eight patients with severe emphysema and six control subjects was evaluated at the time of tissue procurement (ex vivo) and after two weeks of culture with interleukin-2 (in vitro). Junctional region nucleotide sequencing of expanded TCR V{beta} subsets was performed. Results: No significantly expanded TCR V{beta} subsets were identified in ex vivo samples. However, T cells grew from all emphysema (n = 8) but from only one of the control lung samples (n = 6) when exposed to interleukin-2 (p = 0.0013). Within the cultured cells, seven major CD4-expressing TCR V{beta} subset expansions were identified from five of the emphysema patients. These expansions were composed of oligoclonal populations of T cells that had already been expanded in vivo. Conclusion: Severe emphysema is associated with inflammation involving T lymphocytes that are composed of oligoclonal CD4+ T cells. These T cells are accumulating in the lung secondary to conventional antigenic stimulation and are likely involved in the persistent pulmonary inflammation characteristic of severe emphysema.
Key words: Pulmonary disease, chronic obstructive; Lymphocytes; Antigens




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