Airway infection in stable lung transplant patients is associated with decreased intracellular T-helper type 1 pro-inflammatory cytokines in bronchoalveolar lavage T-cell subsets.
Current immunosuppression protocols to prevent lung transplant rejection reduce pro-inflammatory and T-helper type 1 (Th1) cytokines. However, Th1 T-cell pro-inflammatory cytokine production is important in host defense against bacterial infection in the lungs. Excessive immunosuppression of Th1 T-cell pro-inflammatory cytokines leaves patients susceptible to infection. To investigate whether pulmonary infection in lung transplant recipients is associated with reduced Th1 T-cell pro-inflammatory cytokines, whole blood and bronchoalveolar lavage (BAL) fluid from 13 stable lung transplant patients with 'culture-negative' BAL and 13 patients with 'culture-positive' BAL was stimulated in vitro, and cytokine production by CD8+ and CD4+ T-cell subsets was determined using multiparameter flow cytometry. In BAL samples, there was a significant decrease in interleukin-2 (IL2) in CD3+ T cells and tumor necrosis factor-alpha (TNF-alpha) in CD8+ T cells (but not CD4+) in 'culture-positive' compared with 'culture-negative' transplant patients. There was no difference in blood Th1 T-cell cytokines between 'culture-positive' compared with 'culture-negative' transplant patients. A decrease in Th1 cytokines IL-2 and TNF-alpha in BAL T-cell subsets is associated with isolation of potentially pathogenic organisms in the lungs in stable lung transplant patients. Excessive immunosuppression of these Th1 T-cell pro-inflammatory cytokines in stable transplant patients may leave them susceptible to infection. Modifying immunosuppression by monitoring intracellular Th1 pro-inflammatory cytokines in BAL T cells may help to improve morbidity and infection rates in stable lung transplant patients.
Hodge
G
G
Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia. greg.hodge@cywhs.sa.gov.au
Hodge
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Reynolds
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Holmes
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D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology* / Q000276:immunology*; D001999:Bronchoscopy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D016207:Cytokines / Q000032:analysis* / Q000276:immunology; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D016867:Immunocompromised Host; D007376:Interleukin-2 / Q000276:immunology; D008171:Lung Diseases / Q000276:immunology*; D016040:Lung Transplantation / Q000276:immunology; D008297:Male; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D014181:Transplantation Immunology; D014409:Tumor Necrosis Factor-alpha
D016207:Cytokines; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha