ICOS-LICOS interaction is critically involved in TGN1412-mediated T-cell activation
| Autor: | Linda Y. Semmler, Zoe Waibler, Ulrich Kalinke, Sabrina Weissmüller, Jan Müller-Berghaus, Stefan Christians |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
T-Lymphocytes
medicine.medical_treatment T cell Immunology Drug Evaluation Preclinical Cell Communication Biology Antibodies Monoclonal Humanized Lymphocyte Activation Biochemistry Inducible T-Cell Co-Stimulator Protein Inducible T-Cell Co-Stimulator Ligand Interleukin 21 Human Umbilical Vein Endothelial Cells medicine Humans Cytotoxic T cell IL-2 receptor Antigen-presenting cell Cells Cultured Cell Proliferation CD40 ZAP70 Cell Biology Hematology Molecular biology Coculture Techniques Cell biology Cytokine medicine.anatomical_structure biology.protein Cytokines Protein Binding |
| Zdroj: | Blood. 119:6268-6277 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2011-12-401083 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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