ICOS-LICOS interaction is critically involved in TGN1412-mediated T-cell activation

Weissmüller, Sabrina; Semmler, Linda Y.; Kalinke, Ulrich; Christians, Stefan; Müller-Berghaus, Jan; Waibler, Zoe

doi:10.1182/blood-2011-12-401083

Cited by 26T-cell and B-cell ImmunologyMonoclonal and Polyclonal Antibodies ResearchCell Adhesion Molecules Research

ICOS-LICOS interaction is critically involved in TGN1412-mediated T-cell activation

Weissmüller, Sabrina, Semmler, Linda Y., Kalinke, Ulrich, Christians, Stefan, Müller-Berghaus, Jan, Waibler, Zoe·2012·Blood

DOI 10.1182/blood-2011-12-401083

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Abstract

TGN1412, a superagonistic CD28-specific antibody, was shown to require Fc-cross-linking or immobilization as a prerequisite to mediate T-cell proliferation and cytokine release in vitro. We used primary human umbilical vein endothelial cells (HUVECs) to study their ability to induce activation of TGN1412-treated T cells. We confirmed that peripheral primary human T cells do not show activation upon stimulation with soluble TGN1412 alone. Nevertheless, cocultivation of TGN1412-treated T cells with HUVECs induced T-cell activation that was further enhanced using cytokine prestimulated HUVECs. Unexpectedly, Fc-FcγR interaction was dispensable for endothelial cell–mediated proliferation of TGN1412-treated T cells. Transwell-culture assays showed that TGN1412-treated T cells need direct cell-to-cell contact to HUVECs to induce proliferation. We found that costimulatory ICOS-LICOS interaction between T cells and endothelial cells is critically involved in TGN1412-mediated effects. Blocking LICOS reduced TGN1412-mediated T-cell proliferation significantly, whereas recombinant LICOS fully conferred TGN1412-mediated T-cell proliferation. Of note, cytokine stimulation enhanced LICOS expression on HUVECs and ICOS-LICOS interaction up-regulated ICOS expression on TGN1412-treated T cells. Hence, we provide a model of positive feedback conferred by ICOS-LICOS interaction between TGN1412-treated T cells and endothelial cells.

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Endothelial cells first activated by proinflammatory cytokines can restore the in vitro TGN1412 response, suggesting that inflamed endothelium contributes to propagation rather than initiation of the cytokine release syndrome.
“One exception is the ability of endothelial cells first activated by proinflammatory cytokines to restore the in vitro TGN1412 response, suggesting a contribution of inflamed endothelium to the propagation, rather than the initiation, of the CRS [44].”
From The rise and fall of the <scp>CD</scp> 28 superagonist <scp>TGN</scp> 1412 and its return as <scp>TAB</scp> 08: a personal account (2016) · cites this paper as [44]

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Upregulation of FcγRIIb on monocytes is necessary to promote the superagonist activity of TGN1412
Hussain, K., Hargreaves, C. E., Roghanian, A., Oldham, R. J., Chan, H. T. C., Mockridge, C. I., Chowdhury, F., Frendéus, B., Harper, K., Strefford, J. C., et al. (2014) · Blood · doi:10.1182/blood-2014-08-593061 · Cited by 55 · see citing works
Preculture of PBMCs at high cell density increases sensitivity of T-cell responses, revealing cytokine release by CD28 superagonist TGN1412
Römer, P. S., Berr, S., Avota, E., Na, S.-Y., Battaglia, M., ten Berge, I., Einsele, H., & Hünig, T. (2011) · Blood · doi:10.1182/blood-2010-12-319780 · Cited by 153 · see citing works

Authors: Weissmüller, S., Semmler, L. Y., Kalinke, U., Christians, S., Müller-Berghaus, J., & Waibler, Z.
Affiliations: Paul Ehrlich Institut (DE)
Medizinische Hochschule Hannover (DE)
Division of Immunology, Paul Ehrlich Institut, Langen, Germany
ORCID: Kalinke, Ulrich
Waibler, Zoe
Venue: Blood
Publisher: American Society of Hematology
Published: 2012-06-28
Volume: 119
Issue: 26
Pages: 6268-6277
ISSN: 0006-4971 (ISSN-L)
1528-0020
DOI: 10.1182/blood-2011-12-401083
OpenAlex: W2014787310
Cited by: 26
References: 43
Citations by year: 2026: 1 · 2025: 2 · 2024: 1 · 2023: 1 · 2021: 3 · 2019: 1 · 2018: 1 · 2016: 3 · 2015: 4 · 2014: 6 · 2013: 2 · 2012: 1
FWCI: 1.81
Type: journal article
Language: en
Open access: closed
Locations: Blood (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Keywords: TGN1412, T cell activation, endothelial cells, costimulation, T cell proliferation, cell-cell contact, positive feedback, cytokine induction
MeSH terms: Cell Communication, Cells, Cultured, Drug Evaluation, Preclinical, Humans, Lymphocyte Activation, Protein Binding, T-Lymphocytes, Cytokines, Coculture Techniques, Cell Proliferation, Inducible T-Cell Co-Stimulator Protein, Inducible T-Cell Co-Stimulator Ligand, Antibodies, Monoclonal, Humanized, Human Umbilical Vein Endothelial Cells

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ICOS-LICOS interaction is critically involved in TGN1412-mediated T-cell activation

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