Vol 14: Targeting peripheral blood pro-inflammatory cytotoxic lymphocytes by inhibiting CD137 expression: novel potential treatment for COPD.Reportar como inadecuado



 Vol 14: Targeting peripheral blood pro-inflammatory cytotoxic lymphocytes by inhibiting CD137 expression: novel potential treatment for COPD.


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This article is from BMC Pulmonary Medicine, volume 14.AbstractBackground: 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.



Autor: Hodge, Greg; Holmes, Mark; Jersmann, Hubertus; Reynolds, Paul N; Hodge, Sandra

Fuente: https://archive.org/







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