Dynamic changes in myeloid derived suppressor cell subsets following renal transplant: A prospective study

• Published in: Transplant immunology Vol. 32; no. 3; pp. 164 - 171
• Main Authors: Hock, Barry D, McKenzie, Judith L, Cross, Nicholas B, Currie, Margaret J
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2015
• Subjects: Adult; Allergy and Immunology; Allografts - immunology; Cell Count; Dendritic cells; Dendritic Cells - immunology; Flow cytometry; Follow-Up Studies; Humans; Immune Tolerance; Immunity, Cellular; Kidney Transplantation; Male; Middle Aged; Myeloid Cells - immunology; Myeloid-derived suppressor cells; Prospective Studies; Renal transplantation; Tissue Donors; Transplant Recipients; Flow cytometry; MDSC; renal transplant recipients; G-MDSC; myeloid-derived suppressor cells; granulocytic myeloid-derived suppressor cells; RTR; normal blood donors; SCC; dendritic cells; Mo-MDSC; Renal transplantation; cutaneous squamous cell carcinoma; monocytic myeloid-derived suppressor cells; NDs; DC; Dendritic cells; Myeloid-derived suppressor cells
• ISSN: 0966-3274; 1878-5492
• DOI: 10.1016/j.trim.2015.05.001

Abstract Background Myeloid-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. Methods The 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 1 year post-transplant. Results In RTRs, numbers of both G-MDSC and Mo-MDSC increased rapidly following transplant and peaked within 8 days, whilst DC numbers decreased. A second peak in G-MDSC numbers was observed in 7/8 patients within 3 months 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. Conclusions In 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.