INHIBITION OF EAE W/ MONOCLONAL ANTIBODY THAT RECOGNIZES NOVEL ANTIGEN

实验性过敏性脑脊髓炎（EAE），用于动物实验

Experimental allergic encephalomyelitis (EAE), used as an animal model of multiple sclerosis (MS), can be induced by the adoptive transfer of CD4+ T cells that are specific for central nervous system (CNS) antigens While the mechanism(s) responsible for the pathological changes in EAE and MS are not fully defined, the traffic of lymphocytes through the CNS and antigen presentation within the CNS are required events for the development of inflammation Several studies using monoclonal antibodies (mAb) against known molecules expressed on T cells, endothelial cells, or CNS glial cells, have shown that it is possible to inhibit the induction of CNS inflammation in the EAE model In the present study we report a mAb TLD-4A2, obtained by immunizing mice with rat microglia, that recognizes a previously uncharacterized molecule The TLD-4A2 mAb stains resting and activated lymphocytes, as well as activated CNS endothelial cells and microglia The staining pattern of this antibody when screened on tissues from the CNS, lymph node, thymus, and spleen, and by immune- precipitation studies followed by one and two dimension western blots, suggest that it recognizes a novel antigen Treatment of rats with the purified 4A2 mAb resulted in either total inhibition of EAE or a significant delay in its induction and a milder clinical disease TLD-4A2 treatment also resulted in a decreased number T cells and monocyte/macrophages accumulating within perivascular cuffs and penetrating into the CNS parenchyma TLD-4A2 antibody apparently does not directly interfere with T cell function or viability as demonstrated by the ability to recover and stimulate CD4+ encephalitogenic peptide specific T cells from cervical lymph nodes of 4A2 treated animals, and from antibody containing T cell proliferation assays These data suggest that the TLD-4A2 mAb recognizes a novel molecule expressed on lymphocytes, endothelial cells, and macrophages that may play a role in hemato genous cell traffic and the initiation of CNS inflammation