Phenotyping of virus-specific CD8+ effector T-cells over the course of primary EBV infection and the development of PTLD in renal transplant recipients

Primary Epstein-Barr virus (EBV) infection can lead to post-transplantation lymphoproliferative disorder (PTLD) following renal transplantation (RTx). Despite EBV-driven PTLD (ePTLD) being rare, it is potentially lethal. CD8+ T-cells play a crucial role in controlling viral infections and malignant transformation of cells. We therefore hypothesized that aberrant EBV-specific CD8+ T cell maturation may contribute to ePTLD development. We performed multichannel flow cytometry on MHC class I tetramer-isolated EBV-specific CD8+ T-cells targeting lytic EBV BZLF1/BMLF1 and latent LMP2 proteins. This pilot study characterized differentiation markers, cytotoxicity, and inhibitory receptor expression in circulating EBV-specific CD8 T cells from renal transplant recipients (RTRs) with primary EBV infection and those who developed ePTLD, and compared them to RTRs with latent (inactive) EBV infection and healthy individuals (HIs). We demonstrated that RTRs with primary EBV infection display adequate cellular proliferation, development of effector memory differentiation, and expression of granzyme B and K (GrmB and K) despite immunosuppression. RTRs who developed ePTLD showed a delayed seroconversion, an early viral load peak, and altered effector-memory differentiation.