Bootcongres

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-bet^lo/intEomes^lo expression, while intermediate (CD28^-CD27⁺CD127^+/-granzymeB^+/-) Epstein-Barr virus (EBV)- and late (CD28^-CD27^-CD127^-granzyme B⁺) cytomegalovirus (CMV)-specific cells showed a T-bet^intEomes^hi and T-bet^hiEomes^hi/lo expression, respectively (1). 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 RPP-specific cells, since the former displayed a T-bet^hiEomes^int expression, while the latter two were T-beti^ntEomes^hi  and T-bet^lo/intEomes^hi. After control of the virus, 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: T-bet seems particularly important for the generation of CMV-specific effector cells, while Eomes is for EBV-specific effector cells. Thus, the generation of CMV memory cells appears to rely on both T-bet and Eomes expression, whereas Eomes was much more important for EBV-specific memory cells. 

¹. van Aalderen MC, Remmerswaal EB, Heutinck KM, ten Brinke A, Pircher H, van Lier RA and ten Berge IJ. Phenotypic and Functional Characterization of Polyomavirus BK VP1-specific CD8+ T Cells in Healthy Adults. J Virol. 2013 Sep;87(18):10263-72.