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Differential dynamics of donor DC and non-DC peripheral blood mononuclear cell microchimerism in lung transplantation
Authors:Joel Van der Meulen  Nicole A Mifsud  Diahnn Abud  Eldho Paul  Michael D Varney  Sharon R Lewin  Paul U Cameron  Tom C Kotsimbos  
Institution:aDepartment of Medicine, Monash University, Melbourne, Australia;bVictorian Transplantation and Immunogenetics Service, Melbourne, Australia;cDepartment of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Melbourne, Australia;dInfectious Diseases Unit, The Alfred Hospital, Melbourne, Australia;eDepartment of Immunology, Monash University, Melbourne, Australia;fMonash Institute of Health Services Research, school of Public Health and Preventative Medicine, Monash University, Australia
Abstract:Donor cell microchimerism induces tolerance in animal models and may increase graft survival in man. Since dendritic cells (DC) are critical for induction of both tolerance and alloreactivity we developed a method to quantitate microchimerism in donor DC and non-DC in peripheral blood mononuclear cells (PBMC) after lung transplantation. Longitudinal analysis of donor cell microchimerism in eleven sex mismatched lung transplant recipients (LTR) up to 12 months post-transplant used Y chromosome based real-time PCR on sorted cells. Total DC or a proportion of DC subsets in PBMC did not change but there were heterogeneous and dynamic changes in microchimerism in DC and non-DC. Analysis of changes in DC using a mixed model analysis showed significantly less reduction in DC compared to non-DC over time (0.49, p = 0.001). Preferential DC persistence compared to non-DC may indicate tolerance induction but future studies are required to determine if DC microchimerism after transplantation affects clinical outcomes.
Keywords:Dendritic cells  Lung transplantation  Microchimerism  Tolerance
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