Acute lung transplant rejection is associated with localized increase in T-cell IFN gamma and TNF alpha proinflammatory cytokines in the airways

Hodge, Greg, Hodge, Sandra, Chambers, Daniel, Reynolds, Paul N. and Holmes, Mark (2007) Acute lung transplant rejection is associated with localized increase in T-cell IFN gamma and TNF alpha proinflammatory cytokines in the airways. Transplantation, 84 11: 1452-1458.


Author Hodge, Greg
Hodge, Sandra
Chambers, Daniel
Reynolds, Paul N.
Holmes, Mark
Title Acute lung transplant rejection is associated with localized increase in T-cell IFN gamma and TNF alpha proinflammatory cytokines in the airways
Journal name Transplantation   Check publisher's open access policy
ISSN 0041-1337
Publication date 2007-12
Sub-type Article (original research)
DOI 10.1097/01.tp.0000290679.94163.e1
Volume 84
Issue 11
Start page 1452
End page 1458
Total pages 7
Place of publication Philadelphia, PA, United States
Publisher Lippincott Williams & Wilkins
Language eng
Formatted abstract BACKGROUND. Allograft rejection remains a major cause of morbidity and mortality after lung transplantation and is associated with increased gene expression for proinflammatory cytokines. T cells are a major cell type involved in graft rejection. There have been no previous studies of cytokine production by T cells from blood, bronchoalveolar lavage (BAL), and intraepithelial T cells from bronchial brushings (BB) during rejection episodes; we hypothesized that T-cell proinflammatory cytokines would be increased in the airways during rejection episodes despite standard immunosuppression regimens. METHOD. To investigate changes in cytokine profiles during rejection episodes, whole blood, BAL, and BB from stable lung transplant patients and those with acute rejection were stimulated in vitro and intracellular cytokine production by CD8- (CD4+) and CD8+ T-cell subsets determined using multiparameter flow cytometry. RESULTS. Transforming growth factor (TGF)-β was significantly decreased in blood CD4+ and CD8+ T cells while interferon (IFN)-γ and tumor necrosis factor (TNF)-α were significantly increased in BAL CD4+ and CD8+ T cells in patients with evidence of rejection. There was no change in CD4:CD8, interleukin (IL)-2, or IL-4 between stable and rejecting groups. CONCLUSIONS. Acute lung transplant rejection is associated with decreased intracellular T-cell TGFβ in blood and increased intracellular IFNγ and TNFα in BAL CD4+ and CD8+ T cells. Drugs that effectively reduce airway T-cell IFNγ and TNFα proinflammatory cytokine production may improve current protocols for reducing acute graft rejection in lung transplant patients.
Keyword Lung transplant
Rejection
Bronchoalveolar lavage
Flow cytometry
Intracellular proinflammatory cytokines
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
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