Disengaging the IL-2 receptor with daclizumab enhances IL-7-mediated proliferation of CD4(+) and CD8(+) T cells
Allograft rejection is mainly driven by the production of IL-2, which expands T cells by linking the IL-2 receptor (IL-2R) composed of three subunits: CD25, CD122 and CD132. Daclizumab, widely used in immunosuppression, is a humanized anti-CD25 antibody that disrupts IL-2 signaling by binding to CD25 and preventing the assembly of the high-affinity IL-2R. Here we show that Daclizumab, while blocking the T-cell response to IL-2, increases CD4(+) and CD8(+) T-cell proliferative response to the homeostatic cytokine IL-7. The IL-7R shares CD132 with the IL-2R and blocking of CD25 by Daclizumab results in the enhanced formation of the IL-7R that in turn allows IL-7 to bind more efficiently on the cell surface. The consequently increased IL-7R signaling boosts intracellular phosphorylated STAT5 and T-cell proliferation. In addition, treatment with Daclizumab delays the internalization of CD127 upon IL-7 treatment, retaining T-cell sensitivity to IL-7 for a prolonged time. This effect of Daclizumab highlights the redundancy of the cytokine system, which may influence T-cell proliferation in transplanted patients, and provides information to improve future immunosuppressive strategies.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2009 |
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| Erschienen: |
2009 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
|---|---|
| Enthalten in: |
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons - 9(2009), 12 vom: 30. Dez., Seite 2727-35 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Monti, P [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 15.03.2010 Date Revised 24.01.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/j.1600-6143.2009.02825.x |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM191680168 |
|---|
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| 100 | 1 | |a Monti, P |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Disengaging the IL-2 receptor with daclizumab enhances IL-7-mediated proliferation of CD4(+) and CD8(+) T cells |
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| 500 | |a Date Completed 15.03.2010 | ||
| 500 | |a Date Revised 24.01.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Allograft rejection is mainly driven by the production of IL-2, which expands T cells by linking the IL-2 receptor (IL-2R) composed of three subunits: CD25, CD122 and CD132. Daclizumab, widely used in immunosuppression, is a humanized anti-CD25 antibody that disrupts IL-2 signaling by binding to CD25 and preventing the assembly of the high-affinity IL-2R. Here we show that Daclizumab, while blocking the T-cell response to IL-2, increases CD4(+) and CD8(+) T-cell proliferative response to the homeostatic cytokine IL-7. The IL-7R shares CD132 with the IL-2R and blocking of CD25 by Daclizumab results in the enhanced formation of the IL-7R that in turn allows IL-7 to bind more efficiently on the cell surface. The consequently increased IL-7R signaling boosts intracellular phosphorylated STAT5 and T-cell proliferation. In addition, treatment with Daclizumab delays the internalization of CD127 upon IL-7 treatment, retaining T-cell sensitivity to IL-7 for a prolonged time. This effect of Daclizumab highlights the redundancy of the cytokine system, which may influence T-cell proliferation in transplanted patients, and provides information to improve future immunosuppressive strategies | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 650 | 7 | |a Antibodies, Monoclonal, Humanized |2 NLM | |
| 650 | 7 | |a IL2RG protein, human |2 NLM | |
| 650 | 7 | |a Immunoglobulin G |2 NLM | |
| 650 | 7 | |a Interleukin Receptor Common gamma Subunit |2 NLM | |
| 650 | 7 | |a Interleukin-2 Receptor alpha Subunit |2 NLM | |
| 650 | 7 | |a Interleukin-7 |2 NLM | |
| 650 | 7 | |a Interleukin-7 Receptor alpha Subunit |2 NLM | |
| 650 | 7 | |a Receptors, Interleukin-7 |2 NLM | |
| 650 | 7 | |a STAT5 Transcription Factor |2 NLM | |
| 650 | 7 | |a Daclizumab |2 NLM | |
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| 700 | 1 | |a Brigatti, C |e verfasserin |4 aut | |
| 700 | 1 | |a Heninger, A K |e verfasserin |4 aut | |
| 700 | 1 | |a Scirpoli, M |e verfasserin |4 aut | |
| 700 | 1 | |a Bonifacio, E |e verfasserin |4 aut | |
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