1. Rosetting T cells in Hodgkin lymphoma are activated by immunological synapse components HLA class II and CD58.
- Author
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Veldman J, Visser L, Huberts-Kregel M, Muller N, Hepkema B, van den Berg A, and Diepstra A
- Subjects
- CD2 Antigens antagonists & inhibitors, CD58 Antigens biosynthesis, CD58 Antigens genetics, CRISPR-Cas Systems, Cell Adhesion, Cell Line, Tumor, Coculture Techniques, Gene Knockout Techniques, Humans, Protein Interaction Mapping, CD4-Positive T-Lymphocytes immunology, CD58 Antigens immunology, Histocompatibility Antigens Class II immunology, Hodgkin Disease immunology, Immunological Synapses immunology, Lymphocyte Activation immunology, Receptors, Antigen, T-Cell immunology, Rosette Formation
- Abstract
A unique feature of Hodgkin lymphoma (HL) is the presence of CD4+ T cells that surround, protect, and promote survival of tumor cells. The adhesion molecules involved in this so-called T-cell rosetting are important components of the immunological synapse (IS). However, it is unknown whether this synapse is fully assembled and leads to T-cell activation by enabling interaction between the T-cell receptor (TCR) and human leukocyte antigen class II (HLA-II). We established a novel rosetting model by coculturing HLA-II-matched peripheral blood mononuclear cells with HL cell lines and showed IS formation with activation of rosetting T cells. HLA-II downregulation by class II transactivator knockout did not affect the extent of rosetting, but almost completely abrogated T-cell activation. Intriguingly, the level of CD58 expression correlated with the extent of rosette formation, and CD58 knockout or CD2 blockade reduced both rosette formation and T-cell activation. The extension of our findings to primary HL tissue by immunohistochemistry and proximity ligation assays showed interaction of CD2 with CD58 and of TCR-associated CD4 with HLA-II. In conclusion, T-cell rosetting in HL is established by formation of the IS, and activation of rosetting T cells critically depends on the interaction of both TCR-HLA-II and CD2-CD58., (© 2020 by The American Society of Hematology.)
- Published
- 2020
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