Bootcongres

Monocyte lineage cells are next to T cells pivotal key players in kidney graft rejection and also in tolerance. Here, we aimed to define the monocyte subset composition and their functional and phenotypic characteristics in kidney transplant recipients longitudinally over time in stable and rejection conditions. Using flow cytometry, the phenotype, activation status and cytokine production capacity of monocytes were determined in a cohort of 30 stable renal transplant recipients at pre-transplantation, 3 and 6 months post-transplantation. In addition, 5 recipients who experienced rejection were studied and compared to non-rejecting controls. We documented decreased absolute numbers of cells in all three monocyte subsets (CD14++16- classical, CD14++16+ intermediate, and CD14+16++ non-classical) in stable kidney transplant recipients after transplantation with a consistently high frequency of CD16+ monocytes at least 6 months post-transplant. During rejection, the frequency of CD16+ monocytes was significantly decreased compared to non-rejecting transplant recipients (p<0.05). The pro-inflammatory cytokine production capability during the post-transplant phase remained as high as at time of transplantation, despite immunosuppressive therapy. At rejection, the percentage of IL-6 and TNF-α producing monocytes was even increased compared to pre-transplantation. Together, our data demonstrate persistent high frequencies of pro-inflammatory CD16+ monocytes with a strong cytokine production potential in stable kidney transplant recipients, indicating a high pro-inflammatory set-point of the monocytic lineage. During rejection, the percentage CD16+ monocytes was significantly decreased in peripheral blood, suggesting recruitment of CD16+ monocytes to the graft.