Abstract
BackgroundMyeloid-derived suppressor cells (MDSC) are powerful suppressors of immune responses. MDSC numbers are increased in some renal transplant recipients (RTR) and there is increasing interest in their potential role in promoting both transplant tolerance and transplant associated malignancy. However the factors influencing MDSC mobilisation are unknown, and the relative temporal changes in the granulocytic (G-MDSC) and monocytic (Mo-MDSC) subsets of MDSC have not been defined. MethodsThe circulating frequencies of MDSC and dendritic cells (DC) were analysed by multicolour flow cytometry in RTR (n=8) prior to transplant and at regular intervals out to 1year post-transplant. ResultsIn RTRs, numbers of both G-MDSC and Mo-MDSC increased rapidly following transplant and peaked within 8days, whilst DC numbers decreased. A second peak in G-MDSC numbers was observed in 7/8 patients within 3months and 2 patients had a further 3rd peak in G-MDSC numbers which, in one patient, corresponded to a rejection event. Mo-MDSC numbers underwent less fluctuation and a subsequent peak in numbers was observed in only 2/8 patients. Respective kidney donors (n=5) underwent only small transient increases in MDSC following surgery. Overall, there was little correlation between increases in MDSC and the occurrence of detectable clinical events or treatment changes. ConclusionsIn RTRs, MDSC numbers increase rapidly and peak following commencement of immunosuppression, but then fluctuate in response to as yet undefined stimuli. Further studies are required to identify the factors modulating MDSC mobilisation.
Published Version
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