Heterogeneity of EBV-specific CD8 T-cell immunity in tissues is based on epitope specificity.

---

Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B167
Abstract ID: 4530

Presenting Author:
Julien Gras , Post-doctoral research fellow at Columbia Univ. Irving Med. Ctr.

Abstract:

Antiviral T-cell immunity in humans is heterogeneous and can persist in multiple tissues sites depending on host factors and viral pathogenesis. Tissue immunity to EBV has not been characterized. We used an ongoing collection of blood and tissue samples (bone marrow, spleen, lung, lymph nodes) from adult organ donors to profile EBV-specific CD8⁺ T-cells. Samples from 22 donors were analyzed using MHC-I multimers complexed with lytic and latent EBV epitopes, followed by high-dimensional flow cytometry. EBV-specific CD8⁺ T-cells were detected in 19/22 individuals across blood and all tissues, with higher reactivities against lytic epitopes. EBV-specific CD8⁺ T-cells were significantly enriched in the CD45RA^-CCR7^- effector memory subset compared to polyclonal CD8⁺ T-cells. EBV-lytic CD8⁺ T-cells were widely distributed, had a higher proportion of CD45RA⁺CCR7^-TEMRA cells compared to latent ones. They harbored a highly activated phenotype (CD38⁺HLA-DR⁺), as well as specific homing factors (CD69⁺CXRX6⁺). On the contrary, EBV-latent CD8⁺ T-cells localized mainly to secondary lymphoid organs where they displayed a more quiescent phenotype (CD28⁺CD127⁺), and express different residency markers (CD69⁺CD103⁺). Our results show that control of EBV infection requires both surveilling and tissue resident memory cells to respond to different types of EBV latency and epitopes. This can inform strategies for promoting immunity targeting EBV-induced pathologies.