Rosetting T cells in Hodgkin lymphoma are activated by immunological synapse components HLA class II and CD58

Johanna Veldman, Lydia Visser, Magdalena Huberts-Kregel, Natasja Muller, Bouke Hepkema, Anke Van den Berg, Arjan Diepstra*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2437-2441
Number of pages5
JournalBlood
Volume136
Issue number21
Early online date26-Jun-2020
DOIs
Publication statusPublished - 19-Nov-2020

Keywords

  • REED-STERNBERG CELLS
  • EXPRESSION
  • RECEPTOR
  • LINES
  • AMPLIFICATION
  • LYMPHOCYTES
  • CYTOMETRY
  • ADHESION
  • REVEALS
  • NODES

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