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

Abstract

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-α (TNF-α) 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-α 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.