Thesis Felipe Vieira Braga
On 8 June 2017 (12:00 hrs) Felipe Vieira Braga defended his thesis 'Transcriptional control of cytotoxic lymphocytes: an unexpected journey with Hobit' at the University of Amsterdam
Promotor: Prof RAW van Lier MD PhD
Copromotor: KPJM van Gisbergen PhD
Venue: Agnietenkapel, Oudezijds Voorburgwal 231, Amsterdam
Viral infections come in all flavours and models. Depending on the country and demographical group, around 40-70% of individuals are seropositive for human cytomegalovirus (HCMV). HCMV infection is asymptomatic in the vast majority of the population, only constituting a serious threat to immunosuppressed individuals. Despite the lack of clinical symptoms, HCMV infection vastly shapes the immune system, specially in the T cell compartment. HCMV infection generates a lifelong specific T cell response with strong cytotoxic potential but limited proliferative capacity. Little is known on how these cells are maintained in a quiescent and nonproliferative state, whilst maintaining a large reserve of cytotoxic granules that enable immediate effector function. These characteristics are highly desirable in vaccination settings. Previous work have demonstrated that vaccines capable of generating HCMV like responses against other pathogens offer long term protection in non-human primate models. Previously, transcriptome analysis have identified Hobit as one of the most differentially expressed gene in HCMV specific cytotoxic CD8 T cells. Here we demonstrate that Hobit expression is restricted to long lived effector CD8 T cells, cytotoxic CD4 T cells and NK cells. Hobit regulates effector functions such as granzyme B and IFN-y production. Hobit is a metabolic suppressor and regulates survival, hence playing an important role in the maintenance of effector lymphocytes. Our findings contribute to better understanding how these cells are generated and maintained, hence supporting future vaccine development.