We don’t know how CD20 antibodies works…but it is depletion of myelin CD8 T cells?


How does B cell depletion work. The Charcot meeting has given us nothing concrete. Is it the production of regulatory B cells or something else? So to keep on the Charcot theme of B cell therapy

Some people say that it is because ocrelizumab/rituximab attacks T cells. In this new study, they look at CD8 T cells and notably myelin reactive T cells. CD8 T cells express more CD20 than other T cells and they suggest that myelin reactive CD20 T cells go down after CD20 depleting antibody treatment. Now the authors do not say that this is the reason why anti-CD20 works, but the inference is clearly there.

This is a possibility, but the easier explanation to me is that it is targeting a B cell population. Why make it complicated when it can be simple? It allows for a meeting that is full of all sorts of unrelated stuff and keeps us all confused?

This paves the way for CD8 specific T cell depletion. This gives me the Willies ,and has nothing to go with males, as it may remove regulatory cells. Look at EAE studies which can show CD8 regulatory cells

If CD20 CD8 T cells (arrow) are the key then these cells need to express CD19 also because CD19 B cell depletion (Inebilizumab) also inhibits MS too, but where is the CD19 on CD8 T cells?

Even with a magnifying glass it is hard to see on T cells, but next experiment to do in MS…..but it has been done thousands of times already. Its call flow cytometry of T and B cells and they don’t

But sure if you collect enough cells you get some CD19+ T cells

Or are they CD3 + B cells or are they bits of crud in the fluid, anyway if real they are a very, very, very tiny population and it they are important they should give you the cause of MS. At least something for the Worlds T cell Immunologists to cling to.

Anti-CD20 therapy depletes activated myelin-specific CD8+ T cells in multiple sclerosis. Sabatino JJ Jr, Wilson MR, Calabresi PA, Hauser SL, Schneck JP, Zamvil SS. Proc Natl Acad Sci U S A. 2019 Nov 20. pii: 201915309.

CD8+ T cells are believed to play an important role in multiple sclerosis (MS), yet their role in MS pathogenesis remains poorly defined. Although myelin proteins are considered potential autoantigenic targets, prior studies of myelin-reactive CD8+ T cells in MS have relied on in vitro stimulation, thereby limiting accurate measurement of their ex vivo precursor frequencies and phenotypes. Peptide:MHC I tetramers were used to identify and validate 5 myelin CD8+ T cell epitopes, including 2 newly described determinants in humans. The validated tetramers were used to measure the ex vivo precursor frequencies and phenotypes of myelin-specific CD8+ T cells in the peripheral blood of untreated MS patients and HLA allele-matched healthy controls. In parallel, CD8+ T cell responses against immunodominant influenza epitopes were also measured. There were no differences in ex vivo frequencies of tetramer-positive myelin-specific CD8+ T cells between MS patients and control subjects. An increased proportion of myelin-specific CD8+ T cells in MS patients exhibited a memory phenotype and expressed CD20 compared to control subjects, while there were no phenotypic differences observed among influenza-specific CD8+ T cells. Longitudinal assessments were also measured in a subset of MS patients subsequently treated with anti-CD20 monoclonal antibody therapy. The proportion of memory and CD20+ CD8+ T cells specific for certain myelin but not influenza epitopes was significantly reduced following anti-CD20 treatment. This study, representing a characterization of unmanipulated myelin-reactive CD8+ T cells in MS, indicates these cells may be attractive targets in MS therapy.

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    • Bits of crud.can mean a speck of dust or cell debris, trogocytosis.is acquiring the receptor, but these are going to be a minor,minor population

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