| Title | Disengaging the IL-2 Receptor with Daclizumab Enhances IL-7-Mediated Proliferation of CD4(+) and CD8(+) T Cells. | | Author(s) | Monti P, Brigatti C, Heninger AK, Scirpoli M, Bonifacio E | | Institution | Immunology of Diabetes Unit and Clinical Transplant Unit, San Raffaele Scientific Institute, Milan, Italy. | | Source | Am J Transplant 2009 Sep 25. | | 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19788505 |
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