Please use this identifier to cite or link to this item:
Scopus Web of Science® Altmetric
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
Statement of
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 (, 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

Files in This Item:
File Description SizeFormat 
hdl_ 93987.pdfPublished version990.39 kBAdobe PDFView/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.