Increased Intracellular Pro- and Anti-inflammatory Cytokines in Bronchoalveolar Lavage T cells of Stable Lung Transplant Patients

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Abstract
Allograft rejection remains a major cause of morbidity and mortality following lung transplantation and is associated with an increased expression of T-cell proinflammatory cytokines. We have recently shown that peripheral blood T-cell proinflammatory cytokine production was significantly reduced in stable lung transplant patients consistent with immunosuppression therapy. However, analysis of inflammatory cytokine profiles in bronchoalveolar lavage (BAL) T cells may be more relevant than peripheral blood T cells for assessing graft status. To investigate the immunomodulatory effects of currently used immunosuppressive regimens on BAL T-cell cytokine production, whole blood and BAL from stable lung transplant patients and control volunteers was stimulated in vitro and cytokine production by CD8+ and CD4+ T-cell subsets determined using multiparameter flow cytometry. There was a significant decrease in T-cell proinflammatory cytokine production in BAL compared with blood from control subjects but not transplant patients. Anti-inflammatory cytokine IL-4 was increased in BAL compared with blood from both groups. There was a significant increase in IFNγ, IL-2, IL-4, TGFβ, and TNFα production by CD8 T cells and IFNγ and TNFα production by CD4 T cells in BAL from transplant patients compared with controls. We have shown decreased T-cell pro- and anti-inflammatory cytokine production in BAL compared with blood in control subjects but not in stable lung transplant patients. Current immunosuppression protocols have limited effect on T-cell proinflammatory cytokine production in BAL but do upregulate anti-inflammatory cytokines IL-4 and TGFβ. Drugs that effectively reduce T-cell proinflammatory cytokine production in BAL may improve current protocols for reducing graft rejection in these patients.

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