Rosetting T cells in Hodgkin lymphoma are activated by immunological synapse components HLA class II and CD58Veldman, J., Visser, L., Huberts-Kregel, M., Muller, N., Hepkema, B., Van den Berg, A. & Diepstra, A., 19-Nov-2020, In : Blood. 136, 21, p. 2437-2441 5 p.
Research output: Contribution to journal › Article › Academic › peer-review
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.
|Number of pages||5|
|Early online date||26-Jun-2020|
|Publication status||Published - 19-Nov-2020|
- REED-STERNBERG CELLS, EXPRESSION, RECEPTOR, LINES, AMPLIFICATION, LYMPHOCYTES, CYTOMETRY, ADHESION, REVEALS, NODES