Pre-Transplant Frequencies of FoxP3+CD25+ in CD3+CD8+ T Cells as Potential Predictors for CMV in CMV-Intermediate Risk Kidney Transplant Recipients

Transpl Int. 2024 May 29:37:12963. doi: 10.3389/ti.2024.12963. eCollection 2024.

Abstract

Cytomegalovirus (CMV) infection detrimentally influences graft survival in kidney transplant recipients, with the risk primarily determined by recipient and donor serostatus. However, recipient CD8+ T cells play a crucial role in CMV control. The optimal preventive strategy (prophylaxis vs. pre-emptive treatment), particularly for seropositive (intermediate risk) recipients, remains uncertain. We investigated CD8+ T cell subpopulation dynamics and CMV occurrence (DNAemia ≥ 100 IU/mL) in 65 kidney transplant recipients, collecting peripheral blood mononuclear cells before (T1) and 1 year after transplantation (T2). Comparing the two timepoints, we found an increase in granulocyte, monocyte and CD3+CD8+ T cells numbers, while FoxP3+CD25+, LAG-3+ and PD-1+ frequencies were reduced at T2. CMV DNAemia occurred in 33 recipients (55.8%) during the first year. Intermediate risk patients were disproportionally affected by posttransplant CMV (N = 29/45, 64.4%). Intermediate risk recipients developing CMV after transplantation exhibited lower leukocyte, monocyte, and granulocyte counts and higher FoxP3+CD25+ frequencies in CD3+CD8+ T cells pre-transplantation compared to patients staying CMV negative. Pre-transplant FoxP3+CD25+ in CD3+CD8+ T cells had the best discriminatory potential for CMV infection prediction within the first year after transplantation (AUC: 0.746). The FoxP3+CD25+ CD3+CD8+ T cell subset may aid in selecting intermediate risk kidney transplant recipients for CMV prophylaxis.

Keywords: biomarker; cytomegalovirus management; immune cells; kidney transplant; valganciclovir.

MeSH terms

  • Adult
  • Aged
  • CD3 Complex / metabolism
  • CD8-Positive T-Lymphocytes* / immunology
  • Cytomegalovirus / immunology
  • Cytomegalovirus Infections* / immunology
  • Cytomegalovirus Infections* / prevention & control
  • Female
  • Forkhead Transcription Factors* / metabolism
  • Graft Survival / immunology
  • Humans
  • Interleukin-2 Receptor alpha Subunit* / metabolism
  • Kidney Transplantation* / adverse effects
  • Male
  • Middle Aged
  • Risk Factors
  • Transplant Recipients

Substances

  • Forkhead Transcription Factors
  • FOXP3 protein, human
  • Interleukin-2 Receptor alpha Subunit
  • CD3 Complex
  • IL2RA protein, human

Grants and funding

The authors declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Austrian National Bank OeNB (Nr.17212 to KE), and by the European Union’s Horizon 2020 research and innovation program under grant agreement number 896932 (TTVguideTX project consortium; consortium lead: Medical University of Vienna, Gregor Bond). It was also supported by an investigator-initiated research grant by Chiesi to KE, the funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication.