TY - JOUR
T1 - Impact of commonly used transplant immunosuppressive drugs on human NK cell function is dependent upon stimulation condition
AU - Meehan, Aislin Clare
AU - Mifsud, Nicole Andrea
AU - Nguyen, Thi Hoang Oanh
AU - Levvey, Bronwyn
AU - Snell, Gregory I
AU - Kotsimbos, Anastase Thomas Christos
AU - Westall, Glen Philip
PY - 2013
Y1 - 2013
N2 - Lung transplantation is a recognised treatment for patients with end stage pulmonary disease. Transplant recipients receive life-long administration of immunosuppressive drugs that target T cell mediated graft rejection. However little is known of the impact on NK cells, which have the potential to be alloreactive in response to HLA-mismatched ligands on the lung allograft and in doing so, may impact negatively on allograft survival. NK cells from 20 healthy controls were assessed in response to Cyclosporine A, Mycophenolic acid (MPA; active form of Mycophenolate mofetil) and Prednisolone at a range of concentrations. The impact of these clinically used immunosuppressive drugs on cytotoxicity (measured by CD107a expression), IFN-? production and CFSE proliferation was assessed in response to various stimuli including MHC class-I negative cell lines, IL-2/IL-12 cytokines and PMA/Ionomycin. Treatment with MPA and Prednisolone revealed significantly reduced CD107a expression in response to cell line stimulation. In comparison, addition of MPA and Cyclosporine A displayed reduced CD107a expression and IFN-? production following PMA/Ionomycin stimulation. Diminished proliferation was observed in response to treatment with each drug.
AB - Lung transplantation is a recognised treatment for patients with end stage pulmonary disease. Transplant recipients receive life-long administration of immunosuppressive drugs that target T cell mediated graft rejection. However little is known of the impact on NK cells, which have the potential to be alloreactive in response to HLA-mismatched ligands on the lung allograft and in doing so, may impact negatively on allograft survival. NK cells from 20 healthy controls were assessed in response to Cyclosporine A, Mycophenolic acid (MPA; active form of Mycophenolate mofetil) and Prednisolone at a range of concentrations. The impact of these clinically used immunosuppressive drugs on cytotoxicity (measured by CD107a expression), IFN-? production and CFSE proliferation was assessed in response to various stimuli including MHC class-I negative cell lines, IL-2/IL-12 cytokines and PMA/Ionomycin. Treatment with MPA and Prednisolone revealed significantly reduced CD107a expression in response to cell line stimulation. In comparison, addition of MPA and Cyclosporine A displayed reduced CD107a expression and IFN-? production following PMA/Ionomycin stimulation. Diminished proliferation was observed in response to treatment with each drug.
UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3605368/pdf/pone.0060144.pdf
U2 - 10.1371/journal.pone.0060144
DO - 10.1371/journal.pone.0060144
M3 - Article
VL - 8
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 3
M1 - e60144
ER -