Please use this identifier to cite or link to this item: http://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.
RMID: 0030021357
DOI: 10.1186/1471-2466-14-85
Appears in Collections:Medicine publications

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