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Patients with end-stage renal disease (ESRD) suffer from a progressively increasing low-grade systemic inflammation, which is associated with higher morbidity and mortality. Regulatory T cells (Tregs) play an important role in regulation of the inflammatory process. Previously, it has been demonstrated that short-chain fatty acids reduce inflammation in the central nervous system in a murine model of multiple sclerosis through an increase in tissue infiltrating Tregs. Here, we evaluated the effect of the short-chain fatty acid propionate on the chronic inflammatory state and T-cell composition in ESRD patients. Analyzing ESRD patients and healthy blood donors before, during, and 60 days after the propionate supplementation by multiparametric flow cytometry we observed a gradual and significant expansion in the frequencies of CD25 high CD127 - Tregs in both groups. Phenotypic characterization suggests that polarization of naïve T cells towards Tregs is responsible for the observed expansion. In line with this, we observed a significant reduction of inflammatory marker CRP under propionate supplementation. Of interest, the observed anti-inflammatory surroundings did not affect the protective pathogen-specific immunity as demonstrated by the stable frequencies of effector/memory T cells specific for tetanus/diphtheria recall antigens. Collectively, our data suggest that dietary supplements with propionate have a beneficial effect on the elevated systemic inflammation of ESRD patients. The effect can be achieved through an expansion of circulating Tregs without affecting the protective pathogen-reactive immunity.

Host protection upon vaccination usually results from the complex interplay of humoral and cellular components of the immune system. Exploring hepatitis B surface antigen (HBsAg)-specific T cell responses and their correlation with humoral responses under immunosuppression, we analyzed 51 renal transplant recipients, differing in HBV vaccine-specific antibody titers (non [NRs]-, low [LRs]-, and high responders [HRs]) and in 22 healthy controls (HCs) in a cross-sectional study. HBsAg-specific T cells were analyzed by flow cytometry according to expression of activation markers CD40L and/or CD69, and the cytokines IFNγ, IL-2, TNFα, and IL-17. No significant differences in responder rate and magnitude of HBsAg-specific T cell responses were found between HCs and HRs. Interestingly, HBsAg-specific Th-cells were also observed in 50% of humoral NRs. Frequencies of HBsAg-specific CD40L+ Th-cells were significantly higher in HRs compared to LRs (p = 0.009) and in LRs in comparison to NRs (p = 0.043). All but NRs showed a predominance of multi-potent HBsAg-specific TNFα+IL-2+ Th-cells. As expected, HBsAg-specific CD8(+) T cells were rarely found. In conclusion, mounting of hepatitis B vaccine-specific T cell responses is possible in kidney transplant recipients despite immunosuppression. Detection of HBV-specific Th-cells in a significant proportion of humoral NRs contributes to the current discussion on conferring immune protection by cellular memory in such patients., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)