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


METHODS
Phenotype, 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.


RESULTS
The 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.


CONCLUSIONS
Our 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.
Department of Nephrology and Transplantation, Erasmus University Medical Center, Rotterdam, The Netherlands.
Elly J F
EJ
Vereyken
Marina D
MD
Kraaij
Carla C
CC
Baan
Farhad
F
Rezaee
Willem
W
Weimar
Kathryn J
KJ
Wood
Pieter J M
PJ
Leenen
Ajda T
AT
Rowshani
D000328:Adult; D000368:Aged; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D042541:Intracellular Space / Q000378:metabolism; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D010641:Phenotype; D017452:Receptors, IgG / Q000378:metabolism*; D055815:Young Adult
D000954:Antigens, Surface; D016207:Cytokines; D017452:Receptors, IgG