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CD20 positive CD8 T cells are a unique and transcriptionally-distinct subset of T cells with distinct transmigration properties

Martijn Vlaming, Vrouyr Bilemjian, Jimena Álvarez Freile, Harm Jan Lourens, Nienke van Rooij, Gerwin Huls, Tom van Meerten, Marco de Bruyn, Edwin Bremer

2021Scientific Reports31 citationsDOIOpen Access PDF

Abstract

The presence of T cells that are dimly positive for the B cell marker CD20 is well-established in autoimmunity and correlates with disease severity in various diseases. Further, we previously identified that the level of CD20-positive T cells was three-fourfold elevated in ascites fluid of ovarian carcinoma patients, together suggesting a role in both autoimmunity and cancer. In this respect, treatment of autoimmune patients with the CD20-targeting antibody Rituximab has also been shown to target and deplete CD20-positive T cells, previously identified as IFN-gamma producing, low proliferative, CD8 cytotoxic T cells with an effector memory (EM) differentiation state. However, the exact phenotype and relevance of CD20-positive T cells remains unclear. Here, we set out to identify the transcriptomic profile of CD20-positive T cells using RNA sequencing. Further, to gain insight into potential functional properties of CD20 expression in T cells, CD20 was ectopically expressed on healthy human T cells and phenotypic, functional, migratory and adhesive properties were determined in vitro and in vivo. Together, these assays revealed a reduced transmigration and an enhanced adhesive profile combined with an enhanced activation status for CD20-positive T cells.

Topics & Concepts

CD20Cytotoxic T cellCD8BiologyImmunologyEffectorAutoimmunityInterleukin 21Cancer researchAntigenAntibodyIn vitroGeneticsCAR-T cell therapy researchImmune Cell Function and InteractionT-cell and B-cell Immunology