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 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.
Katz-Levy
Y
Y
Department of Microbiology-Immunology and Interdepartmental Immunobiology Center, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Neville
K L
KL
Girvin
A M
AM
Vanderlugt
C L
CL
Pope
J G
JG
Tan
L J
LJ
Miller
S D
SD
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018188:Cardiovirus Infections / Q000150:complications / Q000276:immunology*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000276:immunology* / Q000473:pathology; D003711:Demyelinating Diseases / Q000209:etiology / Q000276:immunology* / Q000473:pathology / Q000821:virology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology / Q000821:virology; D000939:Epitopes / Q000276:immunology*; D005260:Female; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D017628:Microglia / Q000276:immunology; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology* / Q000821:virology; D018991:Myelin Proteolipid Protein / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D013116:Spinal Cord / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology; D017945:Theilovirus
D000939:Epitopes; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments