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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 A. K.,
Scirpoli M.,
Bonifacio E.
Publication year - 2009
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2009.02825.x
Subject(s) - daclizumab , il 2 receptor , interleukin 7 receptor , cytokine , t cell , cd8 , interleukin 2 , microbiology and biotechnology , medicine , cytotoxic t cell , immunology , cancer research , monoclonal antibody , biology , immune system , antibody , in vitro , biochemistry
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.