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Time post-lung transplant correlates with increasing peripheral blood T cell granzyme B and proinflammatory cytokines.

Authors
  • Hodge, G
  • Hodge, S
  • Li-Liew, C
  • Chambers, D
  • Hopkins, P
  • Reynolds, P N
  • Holmes, M
Type
Published Article
Journal
Clinical & Experimental Immunology
Publisher
Wiley (Blackwell Publishing)
Publication Date
Sep 01, 2010
Volume
161
Issue
3
Pages
584–590
Identifiers
DOI: 10.1111/j.1365-2249.2010.04186.x
PMID: 20528884
Source
Medline
License
Unknown

Abstract

Immunosuppression therapy following lung transplant fails to prevent chronic rejection/bronchiolitis obliterans syndrome, which we have shown is associated with lack of suppression of peripheral blood T cell granzyme B, interferon (IFN)-γ and tumour necrosis factor (TNF)-α. We hypothesized that these proinflammatory mediators may increase with time post-transplant in otherwise stable patients before clinical signs of declining lung function, and patients experiencing declining lung function would show a further increase in these mediators. Intracellular cytokine profiles and granzyme B were investigated in T cells in whole blood and airways from lung transplant patients using flow cytometry. There was a significant negative correlation between forced expiratory volume in 1 s (FEV(1) ), drug dose and time post-transplant. A significant correlation between increased granzyme B, IFN-γ, interleukin (IL)-2 and TNF-α and time post-transplant was noted in peripheral blood T cells but not lung T cells from stable patients. Patients with similar drug dose but experiencing declining FEV(1) showed a further increase in peripheral blood T cell IFN-γ, IL-2 and TNF-α. Time post-lung transplant correlates with increasing peripheral blood T cell granzyme B and proinflammatory cytokines. Declining FEV(1) is associated with a further increase in these proinflammatory mediators. Drugs that reduce these inflammatory mediators effectively may reduce the incidence of chronic graft rejection.

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