Analysis of the mechanisms involved in functional impairment of cytotoxic T cells during chronic viral infection

• Applicant: Dr. Hans Christian Probst
• Subject Area: Immunology
• Term: from 2010 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 189682984

Functional impairment of virus-specific CTL is a shared characteristic of persistent viral infections suchas HIV, Hepatitis B and Hepatitis C. These infections pose a significant health problem because theyare often lethal due to development of immunopathology, cancer or severe immunodeficiency. Shortlyafter infection, fully functional CTL responses that contribute to virus control are detected, but theygradually loose effector functions in a hierarchical fashion. Prevention of functional impairment inacutely infected individuals or reactivation of functionally impaired CTL in virus carriers such that thevirus is ultimately controlled may be a therapeutic modality to prevent a life-threatening state. Untilnow, therapeutic vaccination is not successful because the mechanisms underlying gradual functionalimpairment are not understood. Current mouse models of persistent virus infections usually requireinfection with unphysiologically high virus doses to establish chronic infections. This leads toimmediate functional impairment of the specific T cells and therefore only poorly reflects the slowprogression of functional impairment found in human chronic infections. In addition, the rapid immunesubversion after high dose infections hardly yields a window to investigate the underlying mechanismor to allow therapeutic intervention.

• DFG Programme: Research Grants