University medical center Göttingen
Neuropathology

Author Of 1 Presentation

Pathogenesis – Immunology Poster Presentation

P0948 - CD20+ T cells emerge from pathogenic B cell- T cell interaction (ID 1685)

Speakers
Presentation Number
P0948
Presentation Topic
Pathogenesis – Immunology

Abstract

Background

B cell depleting anti-CD20 antibodies (ab) are highly effective in multiple sclerosis (MS). Besides B cells, a population of proinflammatory T cells express CD20. The origin of these CD20 positive T cells and whether their depletion contributes to the clinical effect of anti-CD20 is unclear.

Objectives

This study is focused on characterizing CD20+ T cells both in naive and experimental autoimmune encepahalomyelitis (EAE) mice and in humans.

Methods

CD20+ T cells were analyzed for their phenotype, cytokine expression and developmental state using flow cytometry, FACS, ELISA, RT pcr and microscopy. Spleens, inguinal lymph nodes, blood and spinal cord from wild type, 2D2, µMT and CD20KO mice as well as PBMCs from MS patients were examined. Splenoculture and B cell-T cell coculture with 2D2 T cells and various B cells (wt, CD20KO, membrane stained) were used to analyze CD20 content and transfer. EAE was induced by immunization of the mice with CFA and MOG peptide.

Results

When compared to CD20- T cells, CD20+ T cells show enhanced features of pathogenicity both in mice as well as in patients with MS. In wild-type mice, CD20+ T cells expand during EAE, while B cell-deficient mice do not exhibit CD20+ T cells. T cells themselves are not able to generate CD20 and in splenocyte cultures, de novo development of CD20+ T cells is strictly dependent on the presence of B cells expressing CD20. In direct B cell-T cell cocultures, CD20 is transferred from B cells to T cells via trogocytosis. Along the same lines, transfer of CD20 expressing B cells into B cell-deficient mice results in the development of CD20+ T cells.

Conclusions

CD20 on T cells relies on its transfer from B cells via trogocytosis. Thus, T cell CD20 is a marker for their recent activating interaction with a B cell, explaining the pronounced pro-inflammatory phenotype of these T cells. These data suggest that depletion of CD20+ T cells may substantially support the effectiveness of anti-CD20 ab therapy in MS, and their reappearance in the blood may serve as a marker for reemerging pathogenic B cell – T cell interaction.

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