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

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.

CD20+ T cells: an emerging T cell subset in human pathology

“…Since the 1990 s, observations were made, by flow cytometry, that a small percentage of human CD3 + T cells in peripheral blood dimly express CD20 on their surface [ 4 ]. This is in contrast to the traditional bright expression of CD20 found on B cells which are approximately 15-fold brighter by flow cytometry [ 5 ]. CD20 + T cells may range from 1 to 6% of T cells in peripheral blood (PB) of healthy controls (HCs), and do not express any other markers of B cells such as CD19 [ 6 , 7 ].…”

“…However, why they are only selective for CD20 and not any other B cell surface markers is not clear. A later study performed transcriptomic analysis via RNA sequencing revealing activated CD20 + T cells derived from HCs do not upregulate MS4A1 supporting de Bruyn’s theory of trogocytosis [ 5 ].…”

“…After the exclusion of doublets, CD20 + T cells are commonly identified via flow cytometry as CD3 + CD19¯ lymphocytes with dim expression of CD20. They may express CD4, CD8 or neither; but are particularly enriched with CD8 compared to CD20¯ T cells in HCs [ 5 ]. HCs may have around three-quarters of their PB CD3 + CD20 + compartment as CD8 + T cells [ 5 , 16 ], In multiple sclerosis (MS) patients, similar percentages are also seen [ 17 ].…”

“…They may express CD4, CD8 or neither; but are particularly enriched with CD8 compared to CD20¯ T cells in HCs [ 5 ]. HCs may have around three-quarters of their PB CD3 + CD20 + compartment as CD8 + T cells [ 5 , 16 ], In multiple sclerosis (MS) patients, similar percentages are also seen [ 17 ].…”

Immunogenicity of SARS-CoV-2 vaccines in patients with cancer

“…These include, for example, complement activation and subsequent complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and nonclassical apoptosis induced by crosslinking of CD20 molecules [93]. Anti-CD20 treatment has also been shown to cause a marked reduction in numbers of T cells, for example through the off-target depletion of CD20-positive T cells which account for up to 5% of the CD3+ population [94]. Nonetheless, anti-CD20 therapy was not shown to significantly affect T-cell functionality, and patients maintained the ability to mount an effective T-cell response [60,92,95].…”