ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: FR-PO365

Comparative Analysis of Regulatory T Cell Subpopulations in CKD Outpatients and Healthy Controls

Session Information

  • CKD: Mechanisms - II
    November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Negi, Neema, National University of Ireland Galway, Galway, Ireland
  • Cormican, Sarah, National University of Ireland Galway, Galway, Ireland
  • O Coileain, Eanna, National University of Ireland Galway, Galway, Ireland
  • Griffin, Matthew D., National University of Ireland Galway, Galway, Ireland
Background

Regulatory T cells (T-reg) suppress autoimmunity/inflammation and allo-antigen-specific immune response in transplantation. Consequently, ex vivo-expanded T-reg are a promising immunomodulatroy therapy. In CKD/ESRD, circulating T-reg numbers are peserved and can be culture-expanded. Nonetheless, T-reg sub-phenotypes and their relevance to CKD pathophsiology are not fully characterised. We aimed to compare relative proportions and surface phenotype characteristics of circulating T-reg subpopulations in adult CKD outpatients and healthy adults.

Methods

Blood samples and clinical information were provided by CKD outpatients without immune-mediated disease (n=35, eGFR:11-64) and by healthy volunteers (HV, n=20). Multi-color flow cytometry was performed on fresh PBMC for CD4, CD25, CD127 and FoxP3 (to identify T-reg) and for CD45RA, HLA-DR, TNFR2, CCR7, CD62L and CD39 (to define subpoulations and their functional markers).

Results

Peripheral blood CD4+CD25+CD127lo T-reg (confirmed to be FoxP3+) were identified and subdivided into 3 subpopulations based on expression of CD45RA and HLA-DR [RA+DR-, RA-DR+, RA-DR-]. No difference in T-reg frequency (expressed as % of total CD4+ T-cells) was seen between CKD and HV. However, RA-DR- T-reg were proportionately increased and RA+DR- T-reg were proportionately decreased in CKD (p<0.0001), consistent with a relative expantion of "antigen experienced" T-reg. In regard to surface proteins of potential functional importance, the selectin CD62L was expressed at higher level on total T-reg of CKD vs. HC (average MFI 3810 vs 1299, p=0.0002) as well on each of the 3 T-reg subpopulations. In contrast, surface expression of the ectonuclease CD39 (which dephosphorylates ATP and ADP) was lower on total T-reg (average MFI 665 vs 6936, p<0.0001) and was present on lower proportions of RA-DR+ T-reg (average 53.0% vs 87.1%, p=0.001) and RA-DR- T-reg (average 36.6% vs 73.8%, p<0.0001) in CKD vs. HV. Expression of CCR7 and TNF receptor 2 (TNFR2) did not differ for T-reg and T-reg subpopulations of CKD and HV.

Conclusion

Although adults with CKD had comparable blood T-reg numbers compared to HV, they differed in the relative frequencies of CD45RA/HLA-DR-defined T-reg subpopulations and in expression of proteins that could reflect alterations in migration patterns (CD62L) and specific regulatory functions (CD39).

Funding

  • Private Foundation Support