Using transgenic MHC class II/self-peptide reactive cytotoxic T cells as a method of ameliorating established EAE

Abstract

Abstract In multiple sclerosis (MS) CD4+ T cells are thought to coordinate initiation and maintenance of neuroinflammation following recognition of central nervous system (CNS) antigens in the context of MHC class II molecules. Re-activation of these CNS antigen specific CD4+ T cells within the CNS is thought to be crucial to recruitment of secondary immune effector cells and resultant tissue inflammation. MHC class II is thought to be expressed on professional antigen presenting cells (APC) but not on oligodendrocytes and neurons, two cellular targets for MS pathology. Here we examine the use of defined MHC class II/peptide restricted transgenic T cell receptor expression in mature CD8 T cells to generate cytotoxic cells specific for CNS antigen presenting APC. We suggest that auto-antigen/MHC class II specific APC elimination can ameliorate disease while sparing MHC II negative neurons and oligodendrocytes. This study examines a novel potential therapeutic modality for its efficacy in neuroinflammation.