Cytoimitiunotherapy for persistent virus infection reveals a unique clearance pattern from the central nervous system

Abstract

The mechanism(s) by which infectious or malignant material is cleared by the host has long been an area of intensive study. We have used the murine model of infection with lymphocytic choriomeningitis virus (LCMV) to look at immune clearance during persistent infection. LCMV was selected because the mouse is its natural host, it easily induces acute or persistent infection in vivo, and the mechanism by which it is cleared in vivo during acute infection is now well understood^1–8. Clearance, although associated with several antiviral immune effector mechanisms¹, is primarily dependent on the activity of virus-specific cytotoxic T lymphocytes (CTL) restricted by H–2 molecules of the mouse major histocompatibility complex (MHC)^4–8. If these cells fail to generate or are depleted, progression from acute to persistent infection occurs^1,9,10. Here, using molecular probes, we show that viral nucleic acid sequences, viral proteins and infectious materials can be efficiently and effectively cleared by adoptive transfer of antiviral H–2-restricted lymphocytes bearing the Lyt 2⁺ phenotype. Viral materials are cleared from a wide variety of tissues and organs where they normally lodge during persistent infection. Unexpectedly, the mode by which viral materials are removed from the central nervous system (CNS) differed markedly from the mechanism of clearance occurring at other sites. These observations indicate the possible use of adoptive lymphocyte therapy for treatment of persistent infections and suggest that immune clearance of products from the CNS probably occurs by a process distinct from those in other organs.