Mechanisms underlying noncytopathic clearance of a persistent virus infection from the CNS

• Applicant: Dr. Henning Lauterbach
• Subject Area: Immunology
• Term: from 2005 to 2007
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 14515956

Chronic infection of mice with lymphocytic choriomeningitis virus (LCMV) is a model system that has revealed important insights into the failures that occur in the adaptive immune response during viral persistence in multiple tissue compartments, including the immunologically specialized central nervous system (CNS). Importantly, this system has also provided a forum to investigate strategies to purge the host of persistent infections. For example, adoptive transfer of LCMV-specific memory T cells into mice persistently infected with LCMV results in the elimination of virus from all tissue compartments without a substantial amount of cellular damage. The objective of this project is to define the mechanisms underlying noncytopathic clearance of LCMV from a defined tissue compartment (i.e., the CNS) following adoptive transfer of virusspecific T cells. This objective will be completed by monitoring traceable populations of LCMV-specific CD8+ and CD4+ T cells as well as brain-invading dendritic cells (DCs). These cell populations will be monitored by performing flow cytometry as well as stateof- the-art anatomical analyses. Furthermore, the T cell-generated effector molecules present during virus clearance in the brain are going to be determined. The primary focus of this project is the evaluation of the function of DCs during the clearance. Therefore, the role and the phenotypic as well as functional properties of DCs migrating into the CNS of persistently infected mice following adoptive T cell transfer will be studied in greater detail.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Dorian B. McGavern