Abstract Details

Title B Cells Selectively Induce CD8+ MAIT Cell Effector Functions: Implications for Multiple Sclerosis

Topic Multiple Sclerosis

Presentation(s) P3 - Poster Session 3 (12:00 PM-1:00 PM)

Poster/Presentation
Number 9-001

Objective To study potential disease-relevant interactions between B cells and both CD8 MAIT and non-MAIT T cells in multiple sclerosis (MS)

Background B-cell depletion with anti-CD20 antibodies is highly effective in limiting new MS relapses, in part attributed to attenuation of CD4 T-cell responses, reflecting the well-recognized disease-implicated interactions between B cells and CD4 T cells. Curiously, B-cell depletion also attenuates CD8 T-cell responses, suggesting a role for B cell:CD8 T cell interactions in vivo. Both mucosal associated invariant T (MAIT) CD8 and non-MAIT (conventional) CD8T cells have been implicated in MS.

Design/Methods Effects of differentially-activated B cells on CD8 T-cell subsets were initially assessed using in vitro co-cultures within whole peripheral blood mononuclear cells (PBMC) and using purified cell subsets from healthy controls. T cell proliferation, cytotoxicity and cytokine production were assessed by multiparametric flow-cytometry. Validated flow cytometry panels were applied in batch to cryopreserved PBMC from treatment-naïve MS patients prior to and after in vivo anti-CD20 antibody therapy.

Results B cells suppress proliferation of non-MAIT CD8⁺T cells yet significantly promote MAIT cell expansion in vitro. The differential impact on CD8⁺ T cell subsets is influenced by the B cell differentiation stage and mediated by B-cell secreted products. B cells also differentially impact CD8⁺ T-cell subset cytotoxicity and pro-inflammatory cytokine responses. In vivo, treatment with anti-CD20 selectively reduces frequencies and pro-inflammatory responses of MAIT cells, including diminished proliferation, cytotoxicity and pro-inflammatory cytokine production, that mirrors in vitro findings.

Conclusions Our findings implicate disease-relevant in vivo interactions between B cells and CD8⁺ T cells in MS. B cells differentially impact distinct CD8⁺ T cell subsets, selectively inducing of multiple effector responses of CD8⁺MAIT cells. Selective decreases in CD8+ MAIT cell pro-inflammatory functions may contribute to the therapeutic mode of action of anti-CD20 therapy.

Authors/Disclosures
PRESENTER	No disclosure on file
Koji Shinoda, MD, PhD	No disclosure on file
Rui Li (McGill University)	Mr. Li has nothing to disclose.
Amit Bar-Or, MD, FRCPC (University of Pennsylvania)	Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche Genentech. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merk/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for cabaletta. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi/Genzyme. The institution of Dr. Bar-Or has received research support from Novartis. The institution of Dr. Bar-Or has received research support from Biogen. The institution of Dr. Bar-Or has received research support from Roche/Genentech.

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