Th1 and Th17 cells are resistant towards T cell activation-induced downregulation of CD6

Carolin Brück; Viktoria Golumba-Nagy; Shuaifeng Yan; Ruth L Esser; Jan Thiele; David Stahl; Carola Tho Pesch; Eva Steinbach-Knödgen; David M Kofler

doi:10.1016/j.clim.2022.109025

Th1 and Th17 cells are resistant towards T cell activation-induced downregulation of CD6

Clin Immunol. 2022 May:238:109025. doi: 10.1016/j.clim.2022.109025. Epub 2022 Apr 26.

Authors

Carolin Brück¹, Viktoria Golumba-Nagy¹, Shuaifeng Yan¹, Ruth L Esser¹, Jan Thiele¹, David Stahl², Carola Tho Pesch², Eva Steinbach-Knödgen¹, David M Kofler³

Affiliations

¹ Laboratory of Molecular Immunology, Division of Rheumatology and Clinical Immunology, Department I of Internal Medicine, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
² Laboratory of Molecular Immunology, Division of Rheumatology and Clinical Immunology, Department I of Internal Medicine, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany; Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Cologne, Germany.
³ Laboratory of Molecular Immunology, Division of Rheumatology and Clinical Immunology, Department I of Internal Medicine, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany; Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Cologne, Germany. Electronic address: david.kofler@uk-koeln.de.

PMID: 35487454
DOI: 10.1016/j.clim.2022.109025

Abstract

Background: The cell surface molecule CD6 is a modulator of T cell receptor (TCR) signaling. Recently, it has been reported that CD6 is downregulated on CD4+ T cells following T cell activation. This mechanism could limit the efficacy of anti-CD6 therapeutical antibodies.

Methods: We analyzed CD6 expression on activated and non-activated Th1 cells and Th17 cells by flow cytometry.

Results: Our experiments confirmed a significant downregulation of CD6 on IFNγ- and IL17-negative CD4+ T cells from healthy individuals and from patients with rheumatoid arthritis following T cell activation with anti-CD3 and anti-CD28 antibodies. In contrast, CD6 expression remained stable on activated Th17 cells and Th1 cells.

Conclusions: Th1 and Th17 cells are resistant towards T cell activation-induced downregulation of CD6. These findings are relevant for the future development of CD6 targeting therapies and show that CD6 expression is differentially regulated in CD4+ T cell subsets.

Keywords: CD6; Rheumatoid arthritis; T cell receptor; Th1; Th17.

MeSH terms

Antigens, CD*
Antigens, Differentiation, T-Lymphocyte*
CD28 Antigens / metabolism
Down-Regulation*
Humans
Lymphocyte Activation*
Th1 Cells*
Th17 Cells*

Substances

Antigens, CD
Antigens, Differentiation, T-Lymphocyte
CD28 Antigens
CD6 antigen