Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/93987
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Type: | Journal article |
Title: | Targeting peripheral blood pro-inflammatory cytotoxic lymphocytes by inhibiting CD137 expression: novel potential treatment for COPD |
Author: | Hodge, G. Holmes, M. Jersmann, H. Reynolds, P. Hodge, S. |
Citation: | BMC Pulmonary Medicine, 2014; 14(1):85-1-85-11 |
Publisher: | BioMed Central |
Issue Date: | 2014 |
ISSN: | 1471-2466 1471-2466 |
Statement of Responsibility: | Greg Hodge, Mark Holmes, Hubertus Jersmann, Paul N Reynolds and Sandra Hodge |
Abstract: | Background: We have shown that chronic obstructive pulmonary disease (COPD) is associated with increased production of pro-inflammatory cytokines and the cytotoxic mediator, granzyme B by peripheral blood steroid resistant CD28nullCD137 + CD8+ T cells and granzyme B by NKT-like and NK cells. We hypothesized that we could target these pro-inflammatory/cytotoxic lymphocytes by inhibiting co-stimulation through CD137. Methods: Isolated PBMC from patients with COPD and healthy controls were stimulated with phytohaemagglutinin (PHA) ± blocking anti-CD137 ± 10-6 M methylprednislone (MP) (±stimulatory anti-CD137 ± control antibodies). Pro-inflammatory cytokine profiles and expression of granzyme B, by T, NKT-like CD28 ± subsets and NK cells were determined using flow cytometry. Results: There was a significant decrease in the percentage of T, NKT-like subsets and NK cells producing IFNγ, TNFα and granzyme B in all subjects in the presence of anti-CD137 blocking antibody compared with PHA alone (eg, 60% decrease in CD8 + granzyme B + cells) or MP. Stimulatory anti-CD137 was associated with an increase in the percentage of pro-inflammatory/cytotoxic cells. The inhibitory effect of anti-CD137 on IFNγ, TNFα and granzyme B production by CD28null cells was greater than by CD28+ cells. Conclusions: Blocking CD137 expression is associated with downregulation of IFNγ, TNFα and granzyme B by CD8+ T and NKT-like and NK cells. Targeting CD137 may have novel therapeutic implications for patients with COPD. |
Keywords: | COPD; Blocking CD137; CD28null T and NKT-like cells; NK cells; IFNγ and TNFα |
Rights: | © 2014 Hodge et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. |
DOI: | 10.1186/1471-2466-14-85 |
Appears in Collections: | Aurora harvest 2 Medicine publications |
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hdl_ 93987.pdf | Published version | 990.39 kB | Adobe PDF | View/Open |
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