RATIONALE: Within the lungs of patients with severe emphysema, inflammation continues despite smoking cessation. Foci of T lymphocytes in the small airways of patients with emphysema 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 subjects with severe emphysema contain oligoclonal T-cell populations, suggesting their accumulation in response to antigenic stimuli. METHODS: Lung T-cell receptor (TCR) Vbeta repertoire from eight patients with severe emphysema and six control subjects 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-Vbeta subsets was performed. RESULTS: No significantly expanded TCR-Vbeta 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-Vbeta subset expansions were identified from five of the patients with emphysema. 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.
RATIONALE: Within the lungs of patients with severe emphysema, inflammation continues despite smoking cessation. Foci of T lymphocytes in the small airways of patients with emphysema 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 subjects with severe emphysema contain oligoclonal T-cell populations, suggesting their accumulation in response to antigenic stimuli. METHODS: Lung T-cell receptor (TCR) Vbeta repertoire from eight patients with severe emphysema and six control subjects 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-Vbeta subsets was performed. RESULTS: No significantly expanded TCR-Vbeta 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-Vbeta subset expansions were identified from five of the patients with emphysema. 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.
Authors: I Retamales; W M Elliott; B Meshi; H O Coxson; P D Pare; F C Sciurba; R M Rogers; S Hayashi; J C Hogg Journal: Am J Respir Crit Care Med Date: 2001-08-01 Impact factor: 21.405
Authors: Andrew P Fontenot; Laia Gharavi; Sean R Bennett; Scott J Canavera; Lee S Newman; Brian L Kotzin Journal: J Clin Invest Date: 2003-09 Impact factor: 14.808
Authors: Andrew P Fontenot; Lisa A Maier; Scott J Canavera; Tara B Hendry-Hofer; Mark Boguniewicz; Elizabeth A Barker; Lee S Newman; Brian L Kotzin Journal: J Immunol Date: 2002-04-01 Impact factor: 5.422
Authors: Sandra Grumelli; David B Corry; Li-Zhen Song; Ling Song; Linda Green; Joseph Huh; Joan Hacken; Rafael Espada; Remzi Bag; Dorothy E Lewis; Farrah Kheradmand Journal: PLoS Med Date: 2004-10-19 Impact factor: 11.069
Authors: K Hoetzenecker; A Mitterbauer; E Guenova; T Schweiger; P Altmann; M Zimmermann; H Hofbauer; L Beer; W Klepetko; H J Ankersmit Journal: Wien Klin Wochenschr Date: 2013-03-27 Impact factor: 1.704
Authors: Corry-Anke Brandsma; Machteld N Hylkema; Marie Geerlings; Wouter H van Geffen; Dirkje S Postma; Wim Timens; Huib A M Kerstjens Journal: Respir Res Date: 2009-11-12
Authors: Jeanine M D'Armiento; Steven M Scharf; Michael D Roth; John E Connett; Andrew Ghio; David Sternberg; Jonathan G Goldin; Thomas A Louis; Jenny T Mao; George T O'Connor; Joe W Ramsdell; Andrew L Ries; Neil W Schluger; Frank C Sciurba; Melissa A Skeans; Helen Voelker; Robert E Walter; Christine H Wendt; Gail G Weinmann; Robert A Wise; Robert F Foronjy Journal: Respir Res Date: 2009-11-19