Adoptive transfer of EBV specific CD8+ T cell clones can transiently control EBV infection in humanized mice.

• Main Authors: Olga Antsiferova, Anne Müller, Patrick C Rämer, Obinna Chijioke, Bithi Chatterjee, Ana Raykova, Raquel Planas, Mireia Sospedra, Anatoliy Shumilov, Ming-Han Tsai, Henri-Jacques Delecluse, Christian Münz
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2014-08-01
• Series: PLoS Pathogens
• Online Access: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25165855/?tool=EBI

Epstein Barr virus (EBV) infection expands CD8+ T cells specific for lytic antigens to high frequencies during symptomatic primary infection, and maintains these at significant numbers during persistence. Despite this, the protective function of these lytic EBV antigen-specific cytotoxic CD8+ T cells remains unclear. Here we demonstrate that lytic EBV replication does not significantly contribute to virus-induced B cell proliferation in vitro and in vivo in a mouse model with reconstituted human immune system components (huNSG mice). However, we report a trend to reduction of EBV-induced lymphoproliferation outside of lymphoid organs upon diminished lytic replication. Moreover, we could demonstrate that CD8+ T cells against the lytic EBV antigen BMLF1 can eliminate lytically replicating EBV-transformed B cells from lymphoblastoid cell lines (LCLs) and in vivo, thereby transiently controlling high viremia after adoptive transfer into EBV infected huNSG mice. These findings suggest a protective function for lytic EBV antigen-specific CD8+ T cells against EBV infection and against virus-associated tumors in extra-lymphoid organs. These specificities should be explored for EBV-specific vaccine development.