TY - JOUR
T1 - Endogenous presentation of self myelin epitopes by CNS-resident APCs in Theiler's virus-infected mice
AU - Katz-Levy, Yael
AU - Neville, Katherine L.
AU - Girvin, Ann M.
AU - Vanderlugt, Carol L.
AU - Pope, Jonathan G.
AU - Tan, Lit Jen
AU - Miller, Stephen D.
PY - 1999/9
Y1 - 1999/9
N2 - 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-A5+, 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.
AB - 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-A5+, 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.
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U2 - 10.1172/JCI7292
DO - 10.1172/JCI7292
M3 - Article
C2 - 10487774
AN - SCOPUS:0032752573
VL - 104
SP - 599
EP - 610
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 5
ER -