A MONOCLONAL NATURAL AUTOANTIBODY THAT PROMOTES REMYELINATION SUPPRESSES CENTRAL-NERVOUS-SYSTEM INFLAMMATION AND INCREASES VIRUS EXPRESSIONAFTER THEILERS VIRUS-INDUCED DEMYELINATION

We have used an established experimental model of multiple sclerosis t o investigate the potential beneficial relationship between natural au toimmunity and remyelination after central nervous system (CNS) demyel ination, Intracerebral infection of SJL/J mice with Theiler's murine e ncephalomyelitis virus (TMEV) produces chronic, progressive, inflammat ory CNS demyelination, Chronically infected SJL/J mice show minimal sp ontaneous remyelination, which is in part due to a T cell-mediated imm une response inhibiting myelin repair, We previously identified a mono clonal natural autoantibody, designated SCH94.03, that promotes remyel ination when passively transferred to chronically infected SJL/J mice, The mechanism whereby SCH94.03 promotes remyelination is unknown, alt hough previous reports suggest that natural autoantibodies can modulat e immune system function. In this report we demonstrate that treatment with SCH94.03 reduced by 2- to 3-fold the number of CD4(+) and CD8(+) T cells infiltrating the CNS of SJL/J mice chronically infected with TMEV, in the absence of global lymphocyte depletion, Associated with t he decreased inflammation was a 2- to 3-fold increase in virus antigen expression without a significant increase in viral RNA or virus titer s, Treatment with SCH94.03 also suppressed the humoral immune response to a T cell-dependent antigen in chronically infected mice, Immunohis tochemical staining showed that SCH94.03 labeled MHC class II-positive dendritic cells in peripheral lymphoid organs, These results are cons istent with the proposed immunomodulatory function of natural autoanti bodies and suggest that one mechanism whereby SCH94.03 promotes CNS re myelination in chronically infected SJL/J mice is through inhibition o f a pathogenic immune response.