Longitudinal immune profile reveals reduced function of pro-inflammatory monocytes with age following kidney transplantation.
Am J Transplant
; 21(3): 1147-1159, 2021 03.
Article
in En
| MEDLINE
| ID: mdl-32777159
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Monocytes
/
Kidney Transplantation
Type of study:
Risk_factors_studies
Limits:
Adult
/
Aged
/
Humans
Language:
En
Journal:
Am J Transplant
Journal subject:
TRANSPLANTE
Year:
2021
Type:
Article
Affiliation country:
Canada