Acute lung transplant rejection is associated with localized increase in T-cell IFNgamma and TNFalpha proinflammatory cytokines in the airways.
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.


METHODS
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)-beta was significantly decreased in blood CD4+ and CD8+ T cells while interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha 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 TGFbeta in blood and increased intracellular IFNgamma and TNFalpha in BAL CD4+ and CD8+ T cells. Drugs that effectively reduce airway T-cell IFNgamma and TNFalpha proinflammatory cytokine production may improve current protocols for reducing acute graft rejection in lung transplant patients.
Hodge
Greg
G
Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, Australia. greg.hodge@cywhs.sa.gov.au
Hodge
Sandra
S
Chambers
Daniel
D
Reynolds
Paul N
PN
Holmes
Mark
M
D000208:Acute Disease; D000328:Adult; D018893:Bronchoalveolar Lavage; D006084:Graft Rejection / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D016040:Lung Transplantation / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000276:immunology
D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma