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

• Published in: Transplant international 2024-05, Vol.37, p.12963
• Main Authors: Mooslechner, Agnes A, Schuller, Max, Pfeifer, Verena, Klötzer, Konstantin A, Prietl, Barbara, Kirsch, Alexander H, Stiegler, Philipp, Sucher, Robert, Sourij, Harald, Rosenkranz, Alexander R, Eller, Kathrin
• Format: Article
• Language: English
• Subjects: Adult; Aged; biomarker; CD3 Complex - metabolism; CD8-Positive T-Lymphocytes - immunology; Cytomegalovirus - immunology; Cytomegalovirus Infections - immunology; Cytomegalovirus Infections - prevention & control; cytomegalovirus management; Female; Forkhead Transcription Factors - metabolism; Graft Survival - immunology; Health Archive; Humans; immune cells; Interleukin-2 Receptor alpha Subunit - metabolism; kidney transplant; Kidney Transplantation - adverse effects; Male; Middle Aged; Risk Factors; Transplant Recipients; valganciclovir
• ISSN: 1432-2277; 0934-0874; 1432-2277
• DOI: 10.3389/ti.2024.12963

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 ( = 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.