Rationale: Within the lungs of patients with severe emphysema, inflammation continues despite smoking cessation and is characterized by the presence of T lymphocytes (T cells). Disease severity has been associated with increasing numbers of T cells within the small airways and alveolar walls of patients with chronic obstructive pulmonary disease (COPD). At present, the role of the T cell in this persistent inflammation remains unknown. One important question is whether these T cells are accumulating in the lung in response to an antigen or are being nonspecifically recruited. The aim of this study was to determine if T cells recruited to the lungs of subjects with severe emphysema are composed of oligoclonal T-cell populations, suggesting their accumulation in response to conventional antigenic stimuli. Methods: Lung T-cell receptor (TCR) Vβ repertoire from seven patients with emphysema was evaluated at the time of tissue procurement (ex vivo) and after 2 weeks of culture with interleukin-2 (in vitro). Junctional region nucleotide sequencing of expanded TCR Vβ subsets was performed.
Results: No significantly expanded TCR Vβ subsets were identified in ex vivo samples. However, T cells grew from all emphysema (n = 7) but no control (n = 4) lung samples when exposed to interleukin-2. Within the cultured CD4+ T cells, a total of six major TCR Vβ subset expansions were identified in four of the seven patients with emphysema. Importantly, these T-cell expansions contained T-cell clones that had already been expanded in vivo.
Conclusion: From the lungs of subjects with severe emphysema, oligoclonal CD4+ T-cell populations were identified that preferentially proliferated in culture. Oligoclonal populations of T cells within the lungs of patients with severe emphysema suggest that response to an antigen plays an important role in the continuing inflammation characteristic of severe COPD.
Conflict of Interest Statement: A.K.S. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. P.L.S. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. M.T.F. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. G.P.C. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. K.K.B. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. B.L.K. has been an employee of Amgen, Inc., since July 2004. N.F.V. has received $3,000 for consultation service, and $2,500 as lecture fees. He is the recipient of a GlaxoSmithKline research grant for $90,000. A.P.F. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript.