Dynamics of T-bet and Eomes Expression By Virus-Specific CD8+ T-Cells During Primary Epstein-Barr Virus and Cytomegalovirus Infection in a Kidney Transplant Recipient.

Abstract

Introduction: The T-box transcription factors, T-bet and eomesodermin (Eomes) are key regulators of the (virus-specific) CD8+ T cell response. Recently, we showed that CD28+CD27+CD127+granzyme B- polyomavirus BK (BKV) and Influenza-specific memory cells displayed a T-betlo/intEomeslo expression, while CD28-CD27+CD127+/- granzymeB+/- Epstein-Barr virus (EBV)- and CD28-CD27-CD127-granzyme B+ cytomegalovirus (CMV)-specific cells showed a T-betintEomeshi and T-bethiEomeshi/lo expression, respectively. Because these concern non-cycling memory cells we wondered how T-bet and Eomes by virus-specific CD8+ T-cells evolve over the course of infection. Methods: Using CMV-pp65- and EBV-BZLF-1 (lytic)- and EBV EBNA (latent)-epitope-loaded tetramers we tracked T-bet and Eomes in virus-specific CD8+ T-cells over the course of PCR-monitored primary CMV and EBV infection in a kidney transplant recipient. Results: Acute phase CMV specific cells differed in their T-bet/Eomes expression from EBV-BZLF1 specific cells and EBV-EBNA-specific cells, since the first displayed a T-bethiEomesint expression, while the latter two were T-betintEomeshi and T-betlo/intEomeshi, respectively. After control of the infections, CMV-, but not EBV-specific cells T-bet levels showed a decrease in their expression of T-bet, and Eomes levels remained stable in CMV-specific cells, but dropped in the EBV-, and in particular the latent epitope-specific cells. Conclusion: Virus-specific CD8+ T-cells differ in their kinetics of T-bet and Eomes expression over the course of infection: Eomes appears to be particularly important for the generation of EBV-specific cells, while CMV-specific cells were expressing both transcription factors over the course of infection.