Disengaging the IL-2 receptor with daclizumab enhances IL-7-mediated proliferation of CD4(+) and CD8(+) T cells.

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Monti P, Brigatti C, Heninger AK, Scirpoli M, Bonifacio E

Disengaging the IL-2 receptor with daclizumab enhances IL-7-mediated proliferation of CD4(+) and CD8(+) T cells.

Am J Transplant. 2009 Dec;9(12):2727-35. doi: 10.1111/j.1600-6143.2009.02825.x. Epub 2009 Sep 25.

PubMed ID

19788505 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Daclizumab	Interleukin-2 receptor subunit alpha	Protein	Humans	Yes	Antibody	Details