Innate immune control of the oncogenic Epstein Barr virus by natural killer (NK) cells

• Applicant: Dr. Obinna Chijioke
• Subject Area: Immunology
• Term: from 2011 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 200814771

The advent of highly immunodeficient mouse models that reconstitute human immune system components after transfer of hematopoietic progenitor cells opens the unique opportunity to address basic as well as translational questions to the biology of the human immune system in vivo. The guest lab headed by Christian Münz was able to establish engraftment of NSG mice with human CD34+ hematopoietic progenitor cells and consecutive development of functional human multi-lineage immune cells. Using this strategy Münz and colleagues could show that the reconstituted NSG mouse model reproduces key aspects of primary infection by the human oncogenic Epstein Barr virus (EBV) as well as EBV-associated tumors and T-cell mediated immune control thereof. Furthermore, we recently described the human natural killer (NK) cell compartment in reconstituted NSG mice and could demonstrate the functional competence of these innate lymphocytes. Since numerous studies have established the protective role of NK cells in the immune response against infections and cancer in mice, but conclusive evidence of this effect is lacking in humans, we now would like to address the role of human NK cells in vivo in the control of EBV infection and surveillance of EBV-induced tumors. For these studies we will characterize expansion and activation of human NK cell subsets during EBV infection in vivo, deplete or expand them during EBV infection and investigate the effects of these manipulations on viral titer and tumor development as well as characterize differences in T cell-mediated immune control upon these treatments. We think these approaches will allow us in a highly translational setting to contribute substantially to the understanding of the role of human NK cells in the control of EBV infection and tumor surveillance. The results obtained by these studies will likely broaden our insight into potential immunotherapeutic options of NK cells in the fight against viral infection and cancer.

• DFG Programme: Research Fellowships
• International Connection: Switzerland
• Host: Professor Dr. Christian Münz