More MS news articles for June 2002

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

J Virol 2002 Jul;76(13):6577-85
Kang BS, Lyman MA, Kim BS.
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611.

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.