Reduced CD4+ CD25++ CD45RA- Foxp3hi activated regulatory T cells and its association with acute rejection in patients with kidney transplantation

Transpl Immunol. 2020 Jun:60:101290. doi: 10.1016/j.trim.2020.101290. Epub 2020 Mar 30.


Background: It was found that regulatory T cells (Tregs) importantly affect the maintenance of the kidney graft. However, Tregs are a heterogeneous population with less to more suppressive activity. The aim of this study was to determine the effects of different subsets of Tregs, as well as their ratio to effector T cells (Teff), on kidney transplantation outcomes.

Methods: A total of 58 participants were enrolled in this study and divided into four groups: (i) first kidney transplant recipients (stable 1); (ii) second kidney transplant recipients (stable 2); (iii) transplant recipients with acute rejection (AR); and (iv) healthy control subjects. By using flow cytometer, the frequencies of CD4+ CD25++ CD45RA- Foxp3hi activated Tregs (aTregs), CD4+ CD25+ CD45RA+ Foxp3lo resting Tregs (rTregs), CD4+ CD25+ CD45RA- Foxp3lo non-suppressive T cells, CD4+ CD25+ Foxp3- cells Teff, and total Tregs were analyzed in all subjects.

Results: The frequency of aTregs (as well as the ratio of aTregs/Tregs) was significantly lower in the AR patients than the other three groups. In contrast to AR patients, stables 1 and 2 had a higher aTreg/Treg ratio than those in the control group. Although patients with AR had a significantly lower total Tregs than the other three groups, the balance of total Tregs and Teff was similar between patients with and without AR.

Conclusion: Patients with AR had poorer immunoregulatory properties than those with normal graft functioning, as well as those in the control group. These reduced immunoregulatory properties in patients with AR could lead to graft rejection.

Keywords: Activated Tregs; Acute rejection; Effector T cell; Kidney transplantation; Regulatory T cell.

MeSH terms

  • Acute Disease
  • Adult
  • CD4 Antigens / metabolism
  • Female
  • Flow Cytometry
  • Forkhead Transcription Factors / metabolism
  • Graft Rejection / immunology*
  • Humans
  • Immunophenotyping
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Kidney Transplantation*
  • Leukocyte Common Antigens / metabolism
  • Male
  • Middle Aged
  • T-Lymphocytes, Regulatory / immunology*


  • CD4 Antigens
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-2 Receptor alpha Subunit
  • Leukocyte Common Antigens