Selection of and evasion from cytotoxic T cell responses in the central nervous system

Cytotoxic CD8 T lymphocytes (CTLs) are critical for the clearance of noncytopathic viruses from infected cells. This chapter discusses one mechanism used by viruses to persist—namely, the selection of a variant virus in which changes in the sequence of a CTL epitope abrogate recognition. The unique features of cytotoxic CD8 T cell function in the central nervous system (CNS) are discussed. The role of CTL escape mutants in the viral evasion of the immune system and subsequent disease progression in non-CNS infections are summarized. The immune response in the CNS is similar to the response in extraneural tissue, but several aspects of the activation of the immune response, cellular trafficking, and antigen presentation are unique to the CNS. Although the CNS has classically been considered a site of immune privilege, surveillance of the normal CNS by circulating, activated lymphocytes occurs, with a limited number of lymphocytes being present in the normal CNS at any given time. In mice infected with mouse hepatitis virus and in some humans persistently infected with human immunodeficiency virus type1, hepatitis B virus or hepatitis C virus, CTL escape mutants play an important role in virus amplification and disease progression.