The immune system of a species has developed throughout evolution in the face of infectious disease challenges that are specific to each individual species. We study the human immune system and believe that studying it without a pathogen is like studying a receptor without its ligand.
Therefore, we study the human γ-Herpesvirus Epstein-Barr virus. It is one of the most successful pathogens in humans. It infects more than 90% of the human adult population. Despite its strong growth transforming abilities for B and epithelial cells, most infected individuals control latent EBV infection life-long without tumor development. Only a minority of infected individuals develops EBV associated tumors like Hodgkin's disease, nasopharyngeal carcinoma and Burkitt's lymphoma. During the long co-evolution of humans and EBV, the human immune system has learned to control EBV infection to keep the EBV carrier healthy. The virus has learned to persist after infection for the rest of the EBV carrier's life with a finely tuned latent infection program. Therefore, the human tumorvirus EBV has probably shaped the human immune system and the immune response to EBV demonstrates essential components of human immune responses.
We study three aspects of this mostly asymptomatic coexistence of EBV with humans.
- The early innate immune response to EBV at which forefront Natural Killer cells limit viremia before adaptive immunity establishes the tight immune control that keeps EBV carriers disease free for the rest of their lifes.
- The recognition of EBV transformed cells by CD4+ T cells and failure of this recognition in patients that have developed EBV associated tumors.
- The initiation and maintenance of EBV specific immune control. We investigate how EBV specific CD4+ T cells support the maintenance of EBV specific CD8+ T cell memory, and if dendritic cells, in addition to initiating this immune control, are also instrumental in its maintenance.