PLoS ONE (Jan 2013)

A shift towards pro-inflammatory CD16+ monocyte subsets with preserved cytokine production potential after kidney transplantation.

  • Elly J F Vereyken,
  • Marina D Kraaij,
  • Carla C Baan,
  • Farhad Rezaee,
  • Willem Weimar,
  • Kathryn J Wood,
  • Pieter J M Leenen,
  • Ajda T Rowshani

DOI
https://doi.org/10.1371/journal.pone.0070152
Journal volume & issue
Vol. 8, no. 7
p. e70152

Abstract

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BackgroundThe presence of monocyte-macrophage lineage cells in rejecting kidney transplants is associated with worse graft outcome. At present, it is still unclear how the monocyte-macrophage related responses develop after transplantation. Here, we studied the dynamics, phenotypic and functional characteristics of circulating monocytes during the first 6 months after transplantation and aimed to establish the differences between kidney transplant recipients and healthy individuals.MethodsPhenotype, activation status and cytokine production capacity of classical (CD14++CD16-), intermediate (CD14++CD16+) and non-classical (CD14+CD16++), monocytes were determined by flow cytometry in a cohort of 33 healthy individuals, 30 renal transplant recipients at transplantation, 19 recipients at 3 months and 16 recipients at 6 months after transplantation using a cross-sectional approach.ResultsThe percentage of both CD16+ monocyte subsets was significantly increased in transplant recipients compared to healthy individuals, indicative of triggered innate immunity (p≤0.039). Enhanced production capacity of tumor necrosis factor-α, interferon-γ and interleukin-1β was observed by monocytes at transplantation compared to healthy individuals. Remarkably, three months post-transplant, in presence of potent immunosuppressive drugs and despite improved kidney function, interferon-γ, tumor necrosis factor-α and interleukin-10 production capacity still remained significantly increased.ConclusionOur data demonstrate a skewed balance towards pro-inflammatory CD16+ monocytes that is present at the time of transplantation and retained for at least 6 months after transplantation. This shift could be one of the important drivers of early post-transplant cellular immunity.