| First Author | Katz-Levy Y | Year | 1999 |
| Journal | J Clin Invest | Volume | 104 |
| Issue | 5 | Pages | 599-610 |
| PubMed ID | 10487774 | Mgi Jnum | J:57471 |
| Mgi Id | MGI:1344845 | Doi | 10.1172/JCI7292 |
| Citation | Katz-Levy Y, et al. (1999) Endogenous presentation of self myelin epitopes by CNS-resident APCs in Theiler's virus-infected mice [see comments]. J Clin Invest 104(5):599-610 |
| abstractText | The mechanisms underlying the initiation of virus-induced autoimmune disease 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 central nervous system-resident (CNS-resident) antigen-presenting cells (APCs), leading 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 chronic stages of the disease. Relevant to the initiation of virus-induced autoimmune disease, only CNS APCs isolated from TMEV-infected mice with preexisting myelin damage, not those isolated from naive mice or mice with acute disease, were able to endogenously present a variety of proteolipid protein epitopes to specific Th1 lines. These results offer a mechanism by which localized virus-induced, T cell-mediated inflammatory myelin destruction leads to the recruitment/activation of CNS-resident APCs that can process and present endogenous self epitopes to autoantigen-specific T cells, and thus provide a mechanistic basis by which epitope spreading occurs. |
