On the way to targeting memory cells

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Agonistic anti-CD27 antibody ameliorates EAE by suppressing IL-17 production.

Vogel I, Acolty V, Keler T, Goriely S, Leo O, Moser M.Eur J Immunol. 2022. doi: 10.1002/eji.202149698.

CD27/CD70 costimulation enhances T-cell survival, memory formation and Th1-cell differentiation and effector function. In addition to promoting Th1 responses, CD27 signalling has been shown to exert a negative regulatory role on IL-17 production, resulting in increased sensitivity of CD27 KO mice to experimental autoimmune encephalomyelitis (EAE). By inducing EAE in full CD27 KO mice, and in a novel, T-cell specific CD27 KO mouse strain (CD4-Cre x CD27flox/flox ), we demonstrate herein that CD27 engagement by its natural ligand (CD70) suppresses IL-17 production in a cell autonomous fashion. We further show that CD27 engagement by an agonistic antibody given after EAE induction or at symptom onset similarly suppresses IL-17 production by activated CD4+ T cells infiltrating the inflamed central nervous system (CNS) while IFNγ production was unaffected, leading to an amelioration of inflammatory-related symptoms. These findings propose CD27 costimulation as a potential candidate for therapeutic manipulation to treat autoimmune and autoinflammatory diseases characterized by excessive IL-17 production.

Why present this story?

Well it talks about CD27 as a potential target for MS, and it is music to my ears…but perhaps for all the wrong reasons. CD27 is found on a number of T cells and this is the study matter for the paper. They take a non killing CD27 specific antibody and it inhibits EAE…I say yep blocK CD4 T cellls and it inhibits EAE because it is T cell mediated. However CD27 is one of the few markers of memory B cells. So if you chase CD27 T cells, you should affect memory B cells. If you had a depleting antibody if may get rid of memory B cells and some T cells, I would predict this will would work but the antibody in clinical use is not depleting. This called varlilumab. So will this mousey data encourage people to do studies in humans?

I dont’ know

There is no point in doing this study to get an answer in EAE (a) CD27 is not a marker of memory B cells in mice and (b) CD19 depletion in rodents has no to a marginal effect….because EAE is T cell mediated.

Maybe sone company may do it, when we tried to get some funding people, the idea wasn’t liked

CoI None relevant

Disclaimer these are the authors view

About the author

MouseDoctor

6 comments

  • I don’t really see why investigators continue to use mouse EAE when everybody knows it’s a deeply flawed MS animal model. The logical thing would be to develop a new model (https://www.nature.com/articles/emm201488) if animal models are still needed. Experimenters could produce the same effects in animals using a combination of myelotomy and lobotomy. While targeting an intervention against the researchers (1 litre of vodka) or surgical instruments (a blunting stone) will prevent damage to the animals, it’s never going to translate into a remotely effective treatment for pwMS. Unless your neurologist is an alcoholic and starts making much better decisions under the influence of Vodka.

    • We applied for a grant to do it…but it got monstered by the reviewers as they didn’t believe the approach…maybe a study project now

        • It is easy to find out as the supported studies go online…however if the reviews come back to paraphrase “This is SH1 don’t fund” it is hard to support when the people doing the selection are looking for reasons to allocate limited budgets in one way or another. So it is luck of the draw I sometimes feel that it is better that reviewers say nothing when they feel they have to say something. Should I say your ideas are going nowhere fast when I see an EAE grant or just park that thought and judge the science.

          Sometimes I am asked to do reviews for papers where I fundementally disagree with the authors….for this reason some papers I dont review as I always try to be constructive. For some journals where the process it iterative I don’t want to impose my views on others, to get stuff accepted.

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