Journal
RESPIRATORY RESEARCH
Volume 14, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/1465-9921-14-13
Keywords
Chronic obstructive pulmonary disease; CD8+T cells; Toll-like receptors; Lung
Categories
Funding
- Boehringer Ingelheim
- Actelion
- Merit Review Award (CMF)
- Research Enhancement Award Program from the Biomedical Laboratory Research & Development Service, Department of Veterans Affairs
- USPHS [R01 HL082480, K23 HL093351, K24 HL04212]
- Tissue Procurement Core of the University of Michigan Comprehensive Cancer Center [P30 CA46952]
- Lung Tissue Research Consortium (Clinical Centers) [N01 HR046162]
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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-CD3e without or with various TLR ligands. We measured protein expression of IFN-gamma, TNF-alpha, 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-gamma and TNF-.alpha; 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.
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