Rosetting T cells in Hodgkin lymphoma are activated by immunological synapse components HLA class II and CD58
Open Access
- 19 November 2020
- journal article
- research article
- Published by American Society of Hematology in Blood
- Vol. 136 (21), 2437-2441
- https://doi.org/10.1182/blood.2020005546
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.Keywords
This publication has 27 references indexed in Scilit:
- Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphomaBlood, 2010
- Mechanisms for segregating T cell receptor and adhesion molecules during immunological synapse formation in Jurkat T cellsProceedings of the National Academy of Sciences, 2007
- HLA Class II Expression by Hodgkin Reed-Sternberg Cells Is an Independent Prognostic Factor in Classical Hodgkin's LymphomaJournal of Clinical Oncology, 2007
- CD2 and TCR synergize for the activation of phospholipase C 1/calcium pathway at the immunological synapseInternational Immunology, 2007
- Identification and Purification of Classical Hodgkin Cells From Lymph Nodes by Flow Cytometry and Flow Cytometric Cell SortingAmerican Journal of Clinical Pathology, 2006
- Identification and Purification of Classical Hodgkin Cells From Lymph Nodes by Flow Cytometry and Flow Cytometric Cell SortingAmerican Journal of Clinical Pathology, 2006
- Immunosuppressive regulatory T cells are abundant in the reactive lymphocytes of Hodgkin lymphomaBlood, 2004
- Cd2 Sets Quantitative Thresholds in T Cell ActivationThe Journal of Experimental Medicine, 1999
- The Immunological Synapse: A Molecular Machine Controlling T Cell ActivationScience, 1999
- Rosetting and other reactions of the Reed‐Sternberg cellThe Journal of Pathology, 1977