T cells in MS brain


The central nervous system (CNS) features mechanisms to protect against untoward inflammation yet allowing immune surveillance for pathogens. Pappalardo et al. profiled T cells in the cerebrospinal fluid (CSF) of healthy individuals and patients with multiple sclerosis (MS) using single-cell RNA and TCR sequences to define CNS immune homeostasis in both healthy and patients with MS. In healthy individuals, clonally expanded CSF T cells are largely distinct from those found in the blood with effector, IFNg, and tissue adaptation signatures, whereas CSF T cells from patients with MS differ from healthy controls with a gene expression signature consistent with elevated activation and cytotoxicity. These findings provide insight into the unique immune environment in the CSF under normal and disease-associated conditions.

Transcriptomic and clonal characterization of T cells in the human central nervous system.Pappalardo JL, Zhang L, Pecsok MK, Perlman K, Zografou C, Raddassi K, Abulaban A, Krishnaswamy S, Antel J, van Dijk D, Hafler DA.Sci Immunol. 2020 Sep 18;5(51):eabb8786. doi: 10.1126/sciimmunol.abb878

T cells provide critical immune surveillance to the central nervous system (CNS), and the cerebrospinal fluid (CSF) is thought to be a main route for their entry. Further characterization of the state of T cells in the CSF in healthy individuals is important for understanding how T cells provide protective immune surveillance without damaging the delicate environment of the CNS and providing tissue-specific context for understanding immune dysfunction in neuroinflammatory disease. Here, we have profiled T cells in the CSF of healthy human donors and have identified signatures related to cytotoxic capacity and tissue adaptation that are further exemplified in clonally expanded CSF T cells. By comparing profiles of clonally expanded T cells obtained from the CSF of patients with multiple sclerosis (MS) and healthy donors, we report that clonally expanded T cells from the CSF of patients with MS have heightened expression of genes related to T cell activation and cytotoxicity.

What are they killing…oligodendrocytes, nerves or virus?

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  • Does the full article detail other important aspects or findings that aren’t mentioned in the abstract? I’m probably going to just pay for it, maybe it’ll end up being worth it. I’d love to be near an active research center. I’d volunteer to be in probably any study that they’d put me in.

      • Thank you, I’m trying to figure out how to make this one show up. I have 2 boxes full of studies from after I moved a few years ago lol. The only neurologist within hours of where I lived didn’t know anything about MS. Her practice involved people who have migraines and a few people who had Parkinson’s. At least she did actually read them. The one I see now only sees people who have ms, but I don’t know how much research she does on her own now. I don’t think that she does very much.

  • Dear Barts team,

    A pathologist in The Netherlands did research on covid-19 dead people’s brain and cns. All but one had T-cells in their brain and cns. The article states that their shouldn’t be T-cells in any brain, due to blood-brain barrier. They suggest that covid-19 mortality could have something to do with this.

    I’m on Ocrelizumab now, but before I was on Natalizumab. I had to stop Natalizumab due to sudden anti-jcv with a super high titerindex.

    To your knowledge, do you think that its possible for ex-Natalizumab patiënts who tested positive on anti-jcv, to still be at risk for PML when infected with covid-19?

    Thanks and regards

    • When the pathologists are doing the studies…the person is sadly dead and they died of something, and if it was a neurological condition such as covid encephalitis, one would expect T cells to be in the brain. There is a suggestion that it is neurotrophic and one could ask if natalizumab influences the clearing of that virus. However, to date there have been people infected with COVID and they have not dies due to a PML-like syndrome, as fr as I know. Once you stop natalizumab cells can get into the brain within about 8 weeks, so if you have switched then the risk of natalizumab will drop but you gain risk from being on anti-CD20. Based on data presented yesterday there was a suggestion that the increased risk of anti-CD20 is associated with rituximab use rather than ocrelizumab…I am not sure how you explain that bit.

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