Brief Definitive Report INDUCIBILITY OF la ANTIGEN ON ASTROCYTES BY MURINE CORONAVIRUS JHM IS RAT STRAIN DEPENDENT BY PAUL T. MASSA, ROBERT BRINKMANN, AND VOLKER TER MEULEN

Infection of Lewis rats with the murine coronavirus JHM leads to a persistent infection in the central nervous system (CNS) and a disease process that shares some features with experimental allergic encephalomyelitis (EAE) (1-4). After an incubation period of weeks, a subacute demyelinating encephalomyelitis (SDE) develops that is characterized by paralysis (2). Histologically, the main lesion consists of a primary demyelination associated with perivascular cuffings and a cellular infiltration of macrophages as well as helper and cytotoxic T lymphocytes (1, 2) . SDE animals reveal a cell-mediated immune (CMI) response to myelin basic protein (MBP) as documented in adoptive transfer experiments (1) . In addition, genetic experiments demonstrate that Brown-Norway (BN) rats are resistant to SDE, similar to what has been observed in EAE (4) . These findings indicate an immunopathological reaction in coronavirus-induced SDE in Lewis rats that is lacking in BN rats . A CMI response is genetically controlled at at least two levels : (a) the ability of the animal to generate an encephalolytogenic T cell response to antigen within the brain (foreign or autoantigen) from its genetically determined T cell repertoire and (b) the degree to which the antigen is presented to these T cells in the context of class I and II (Ia) histocompatibility molecules within a particular tissue . Class II-restricted T cells initiate an immune response to infection and both class Iand II-restricted T cells provide cytolysis of infected cells (5). Since la molecules are normally lacking on cells of the brain (6), the induction of la within the brain is crucial for the initial local presentation of viral antigen during infection . It may therefore be important that astrocytes of Lewis rat brain can be induced to express la directly by JHM virus (7, 8) as well as by other viruses . IFN-y subsequently released by antigen-activated T cells can further induce the antigen-presenting function of astrocytes (9-11) . The direct induction of la on astrocytes by JHM virus is also thought to play a crucial role in eliciting the excessive T cell response in susceptible rats . Supporting this notion are recent observations by us (12) showing that astrocytes of rat and mouse strains susceptible to EAE express much higher levels of la than astrocytes of resistant strains after treatment with IFN-y. We now extend these studies and analyze JHM virus induction of la on astrocytes of rats susceptible or resistant to SDE and show that, unlike astrocytes of susceptible Lewis rats, induction of astrocyte la by JHM virus is not detectable in the resistant BN rat.