The majority of infiltrating CD8+ T cells in the central nervous system of susceptible SJL/J mice infected with Theiler's virus are virus specific and fully functional.
Theiler's virus infection of the central nervous system (CNS) induces an immune-mediated demyelinating disease in susceptible mouse strains, such as SJL/J, and serves as a relevant infectious model for human multiple sclerosis. It has been previously suggested that susceptible SJL/J mice do not mount an efficient cytotoxic T-lymphocyte (CTL) response to the virus. In addition, genetic studies have shown that resistance to Theiler's virus-induced demyelinating disease is linked to the H-2D major histocompatibility complex class I locus, suggesting that a compromised CTL response may contribute to the susceptibility of SJL/J mice. Here we show that SJL/J mice do, in fact, generate a CD8(+) T-cell response in the CNS that is directed against one dominant (VP3(159-166)) and two subdominant (VP1(11-20) and VP3(173-181)) capsid protein epitopes. These virus-specific CD8(+) T cells produce gamma interferon (IFN-gamma) and lyse target cells in the presence of the epitope peptides, indicating that these CNS-infiltrating CD8(+) T cells are fully functional effector cells. Intracellular IFN-gamma staining analysis indicates that greater than 50% of CNS-infiltrating CD8(+) T cells are specific for these viral epitopes at 7 days postinfection. Therefore, the susceptibility of SJL/J mice is not due to the lack of an early functional Theiler's murine encephalomyelitis virus-specific CTL response. Interestingly, T-cell responses to all three epitopes are restricted by the H-2K(s) molecule, and this skewed class I restriction may be associated with susceptibility to demyelinating disease.
Kang
Bong-Su
BS
Department of Microbiology-Immunology, Northwestern University Medical School, 303 E Chicago Avenue, Chicago, IL 60611, USA.
Lyman
Michael A
MA
Kim
Byung S
BS
D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002213:Capsid / Q000737:chemistry / Q000276:immunology; D018188:Cardiovirus Infections / Q000276:immunology* / Q000821:virology; D002490:Central Nervous System / Q000276:immunology* / Q000821:virology; D020805:Central Nervous System Viral Diseases / Q000276:immunology* / Q000821:virology; D003711:Demyelinating Diseases / Q000821:virology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006183:H-2 Antigens / Q000276:immunology; D016056:Immunodominant Epitopes / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D017945:Theilovirus / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D016056:Immunodominant Epitopes; D010455:Peptides; D007371:Interferon-gamma