Disengaging the IL-2 receptor with daclizumab enhances IL-7-mediated proliferation of CD4+ and CD8+ T Cells

P. Monti, C. Brigatti, A. K. Heninger, M. Scirpoli, E. Bonifacio

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)2727-2735
Number of pages9
JournalAmerican Journal of Transplantation
Issue number12
Publication statusPublished - Dec 2009


  • Immunosuppression
  • T cell
  • Transplant
  • Zenapax

ASJC Scopus subject areas

  • Transplantation
  • Immunology and Allergy
  • Pharmacology (medical)


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