Lung CD8+ T cells in COPD have increased expression of bacterial TLRs

TitleLung CD8+ T cells in COPD have increased expression of bacterial TLRs
Publication TypeJournal Article
Year of Publication2013
AuthorsFreeman CM, Martinez FJ, Han MLK, Washko GR, McCubbrey AL, Chensue SW, Arenberg DA, Meldrum CA, McCloskey L, Curtis JL
JournalRespir Res
Date Published2013
KeywordsAged, CD8-Positive T-Lymphocytes, Cells, Cultured, Female, Gene Expression Regulation, Bacterial, Humans, Lung, Male, Middle Aged, Prospective Studies, Pulmonary Disease, Chronic Obstructive, Toll-Like Receptors

BACKGROUND: Toll-like receptors (TLRs) on T cells can modulate their responses, however, the extent and significance of TLR expression by lung T cells, NK cells, or NKT cells in chronic obstructive pulmonary disease (COPD) is unknown.

METHODS: Lung tissue collected from clinically-indicated resections (n = 34) was used either: (a) to compare the expression of TLR1, TLR2, TLR2/1, TLR3, TLR4, TLR5, TLR6 and TLR9 on lung CD8+ T cells, CD4+ T cells, NK cells and NKT cells from smokers with or without COPD; or (b) to isolate CD8+ T cells for culture with anti-CD3ε without or with various TLR ligands. We measured protein expression of IFN-γ, TNF-α, IL-13, perforin, granzyme A, granzyme B, soluble FasL, CCL2, CCL3, CCL4, CCL5, CCL11, and CXCL9 in supernatants.

RESULTS: All the lung subsets analyzed demonstrated low levels of specific TLR expression, but the percentage of CD8+ T cells expressing TLR1, TLR2, TLR4, TLR6 and TLR2/1 was significantly increased in COPD subjects relative to those without COPD. In contrast, from the same subjects, only TLR2/1 and TLR2 on lung CD4+ T cells and CD8+ NKT cells, respectively, showed a significant increase in COPD and there was no difference in TLR expression on lung CD56+ NK cells. Production of the Tc1 cytokines IFN-γ and TNF-α by lung CD8+ T cells were significantly increased via co-stimulation by Pam3CSK4, a specific TLR2/1 ligand, but not by other agonists. Furthermore, this increase in cytokine production was specific to lung CD8+ T cells from patients with COPD as compared to lung CD8+ T cells from smokers without COPD.

CONCLUSIONS: These data suggest that as lung function worsens in COPD, the auto-aggressive behavior of lung CD8+ T cells could increase in response to microbial TLR ligands, specifically ligands against TLR2/1.

Alternate JournalRespir. Res.
PubMed ID23374856
PubMed Central IDPMC3583694
Grant ListK23 HL093351 / HL / NHLBI NIH HHS / United States
K24 HL04212 / HL / NHLBI NIH HHS / United States
N01 HR046162 / HR / NHLBI NIH HHS / United States
N01 HR046162 / HR / NHLBI NIH HHS / United States
P30 CA46952 / CA / NCI NIH HHS / United States
R01 HL082480 / HL / NHLBI NIH HHS / United States
T32 AI007413 / AI / NIAID NIH HHS / United States