Oligoclonal CD4+ T cells in the lungs of patients with severe emphysema.
BACKGROUND
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.


CONCLUSIONS
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.
Sullivan
Andrew K
AK
Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Simonian
Philip L
PL
Falta
Michael T
MT
Mitchell
John D
JD
Cosgrove
Gregory P
GP
Brown
Kevin K
KK
Kotzin
Brian L
BL
Voelkel
Norbert F
NF
Fontenot
Andrew P
AP
D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology; D005260:Female; D006801:Humans; D008168:Lung / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011656:Pulmonary Emphysema / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology
D016693:Receptors, Antigen, T-Cell, alpha-beta