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Longitudinal immune profile reveals reduced function of pro‐inflammatory monocytes with age following kidney transplantation
Author(s) -
Désy Olivier,
Vallin Patrice,
Béland Stéphanie,
BouchardBoivin François,
Gama Alcino P.,
De Serres Sacha A.
Publication year - 2021
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.16249
Subject(s) - medicine , immunology , cd14 , immune system , immunosuppression , innate immune system , transplantation , cd80 , kidney transplantation , inflammation , tlr4 , monocyte , peripheral blood mononuclear cell , cytotoxic t cell , biology , in vitro , cd40 , biochemistry
Toxicity of immunosuppression, notably the risk of infection, increases with age. However, the dynamic changes in innate immune response following transplantation are unclear. Based on recent observations, we hypothesized that pro‐inflammatory capacity would decrease with age. We analyzed approximately 300 PBMC samples collected longitudinally in 45 de novo, adult kidney recipients and performed detailed phenotypic and functional profiling of monocytes and T cell subsets. Inflammatory response to TLR4 stimulation and indirect allostimulation using mismatched HLA peptides were assessed. In patients aged ≥56 years, TNF‐α production by intermediate monocytes was similar to that in younger patients early posttransplant, but diminished substantially later. Adjusted analyses suggested that this was not attributable to confounding factors. In contrast, the alloimmune response to HLA peptides measured by IFN‐γ in CD4 + T cells and TNF‐α in monocytes was stable over time, but was low in older recipients. Measurement of CD80‐86 surface expression revealed no signal for a lower costimulation capacity of APCs. These results suggest that older recipients have a reduced function of their innate pro‐inflammatory immune cells posttransplant while maintaining a stable, low alloimmune response over time. The effect of reduced immunosuppressant doses on preventing this phenomenon needs to be clarified.