# Pre-transplant IE1-specific T-cell response and CD8+ T-cell count as predictive markers of treated HCMV reactivation in kidney transplant recipients

**Authors:** Federica Zavaglio, Irene Cassanti, Marilena Gregorini, Maria Antonietta Grignano, Teresa Rampino, Daniele Lilleri, Fausto Baldanti

PMC · DOI: 10.3389/fimmu.2025.1538795 · Frontiers in Immunology · 2025-04-16

## TL;DR

This study identifies pre-transplant CD8+ T-cell counts and IE1-specific T-cell responses as potential predictors of HCMV reactivation risk in kidney transplant recipients.

## Contribution

The study introduces pre-transplant CD8+ T-cell count and IE1-specific T-cell response as novel predictive markers for HCMV reactivation in kidney transplant patients.

## Key findings

- Higher CD8+ T-cell counts (≥215 cells/μl) were associated with lower HCMV reactivation risk.
- Patients with IE1-specific T-cell response ≥60 spots had reduced HCMV reactivation and lower DNAemia peaks.

## Abstract

Human cytomegalovirus (HCMV) infection represents a significant complication for kidney transplant recipients (KTRs). The goal of this study was to evaluate potential immunological markers at pre-transplant in HCMV-seropositive KTRs for predicting HCMV severe reactivation (e.g treated HCMV reactivation) during the first year after transplant.

Before transplant, lymphocyte count was measured in whole blood and HCMV-specific T-cell response was determined using ELISpot assay after stimulation with pp65, IE-1 and IE-2 peptides pool. HCMV DNA was monitored during the first year after transplant. Among the 65 KTRs enrolled, 44 (68%) patients had HCMV self-resolving reactivation (Controllers) while 21 (32%) required antiviral treatment for HCMV reactivation (Non-Controllers).

No significant difference in CD4 T-cell count was observed, but Controllers had higher CD8+ T-cell counts compared to Non-Controllers. Based on ROC analysis, a CD8+ T-cell count ≥215 cells/μl was associated with a lower incidence of HCMV reactivation after transplant. Additionally, a higher IE-1-specific T-cell response was observed in Controllers and patients with IE1-specific T-cell response ≥60 spots showed a reduced incidence of HCMV reactivation and lower DNAemia peak.

Lymphocyte counts and HCMV-specific T-cell response can be measured at pre-transplant in KTRs in order to efficiently predict the risk of treated HCMV reactivation during the first year after transplant. Potential cut-off and diagnostics algorithm should be better investigated in a large patients setting.

## Linked entities

- **Proteins:** ie1 (IE1), Lcp1 (lymphocyte cytosolic protein 1), ie2 (integument esterase 2)

## Full-text entities

- **Genes:** CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}
- **Diseases:** HCMV reactivation (MESH:D000085343), infection (MESH:D007239)
- **Species:** Homo sapiens (human, species) [taxon 9606], Human betaherpesvirus 5 (no rank) [taxon 10359]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12040814/full.md

## References

36 references — full list in the complete paper: https://tomesphere.com/paper/PMC12040814/full.md

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Source: https://tomesphere.com/paper/PMC12040814