Endogenous presentation of self myelin epitopes by CNS-resident APCs in Theiler's virus-infected mice

The mechanisms underlying the initiation of virus-induced autoimmune diseas e are not well understood. Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), a mouse model of multiple sclerosis, is initiated by TMEV-specific CD4(+) T cells targeting virally infected centra l nervous system-resident (CNS-resident) antigen-presenting cells (APCs), l eading to chronic activation of myelin epitope-specific CD4(+) T cells via epitope spreading. Here we show that F4/80(+), I-A(s+), CD45(+) macrophages /microglia isolated from the CNS of TMEV-infected SJL mice have the ability to endogenously process and present virus epitopes at both acute and chron ic stages of the disease. Relevant to the initiation of virus-induced autoi mmune disease, only CNS APCs isolated from TMEV-infected mice with preexist ing myelin damage, not those isolated from naive mice or mice with acute di sease, were able to endogenously present a variety of proteolipid protein e pitopes to specific Th1 lines. These results offer a mechanism by which loc alized virus-induced, T cell-mediated inflammatory myelin destruction leads to the recruitment/activation of CNS-resident APCs that can process and pr esent endogenous self epitopes to autoantigen-specific T cells, and thus pr ovide a mechanistic basis by which epitope spreading occurs.