T cells killing the myelin forming cells


In the 1980s to 1990s, following the discovery that gamma interferon could up regulate major histocompatibility class II on cells other than macropages, we had paper after paper of cell type A and Cell type B, etc, etc was the the trigger of autoimmunity, every cell was an antigen presenting cells and even a wellington boot with MHC class II was an antigen presenting cells and could present myelin antigen to CD4 T cells. Astroytes (supporting cell) in the CNS was an antigen presenting cell and in a test tube this could be seen, but there wasa problem with it all and that was when you looked in the brain tssue of animals and humans, these cells simply did not express MHC class II. It is getting to the stage where some people are forgetting CD4 T cells and are turning their attention to CD8 T cells after all they are the dominant cell type the CNS. So off we go again. Here gamma interferon a cytokine that activates macrophages and microglial and upregulates major histocompatibility class I and II, inhibits myelin-precurosr cells as they become targets for CD8 killing. This is the mechanism of how virally infected cells are killed. The virus gets inside the cell. Viral proteins are loaded into MHC class I which is expressed on the cell surface and is a target for viral-specific CD8 T cells. They bind to the MHC class I and viral protein fragments and produce molecules that pump holes into the target and this dies,

Oligodendrocyte precursor cells present antigen and are cytotoxic targets in inflammatory demyelination. Kirby L, Jin J, Cardona JG, Smith MD, Martin KA, Wang J, Strasburger H, Herbst L, Alexis M, Karnell J, Davidson T, Dutta R, Goverman J, Bergles D, Calabresi PA. Nat Commun. 2019 Aug 29;10(1):3887. 

Oligodendrocyte precursor cells (OPCs) are abundant in the adult central nervous system, and have the capacity to regenerate oligodendrocytes and myelin. However, in inflammatory diseases such as multiple sclerosis (MS) remyelination is often incomplete. To investigate how neuroinflammation influences OPCs, we perform in vivo fate-tracing in an inflammatory demyelinating mouse model. Here we report that OPC differentiation is inhibited by both effector T cells and IFNγ overexpression by astrocytes. IFNγ also reduces the absolute number of OPCs and alters remaining OPCs by inducing the immunoproteasome and MHC class I. In vitro, OPCs exposed to IFNγ cross-present antigen to cytotoxic CD8 T cells, resulting in OPC death. In human demyelinated MS brain lesions, but not normal appearing white matter, oligodendroglia exhibit enhanced expression of the immunoproteasome subunit PSMB8. Therefore, OPCs may be co-opted by the immune system in MS to perpetuate the autoimmune response, suggesting that inhibiting immune activation of OPCs may facilitate remyelination.

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  • This seems too simple and logical to have been missed.

    So their conclusion would be to inhibit interferon gamma and killer CD8 T cells.

    Why is there too much interferon gamma produced by astrocytes in MS or is this just in EAE mice?

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