IL-2/anti-IL-2 antibody complexes show strong biological activity by avoiding interaction with IL-2 receptor alpha subunit CD25

Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2171-6. doi: 10.1073/pnas.0909384107. Epub 2010 Jan 19.


IL-2 is crucial to T cell homeostasis, especially of CD4(+) T regulatory cells and memory CD8(+) cells, as evidenced by vigorous proliferation of these cells in vivo following injections of superagonist IL-2/anti-IL-2 antibody complexes. The mechanism of IL-2/anti-IL-2 antibody complexes is unknown owing to a lack of understanding of IL-2 homeostasis. We show that IL-2 receptor alpha (CD25) plays a crucial role in IL-2 homeostasis. Thus, prolongation of IL-2 half-life and blocking of CD25 using antibodies or CD25-deficient mice led in combination, but not alone, to vigorous IL-2-mediated T cell proliferation, similar to IL-2/anti-IL-2 antibody complexes. These data suggest an unpredicted role for CD25 in IL-2 homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Blocking / administration & dosage
  • Antigen-Antibody Complex / metabolism*
  • Half-Life
  • Homeostasis
  • Immunoglobulin G / metabolism
  • Interleukin-2 / immunology*
  • Interleukin-2 / metabolism*
  • Interleukin-2 Receptor alpha Subunit / antagonists & inhibitors
  • Interleukin-2 Receptor alpha Subunit / deficiency
  • Interleukin-2 Receptor alpha Subunit / genetics
  • Interleukin-2 Receptor alpha Subunit / metabolism*
  • Mice
  • Mice, Congenic
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Receptors, Fc / metabolism
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / metabolism


  • Antibodies, Blocking
  • Antigen-Antibody Complex
  • Il2ra protein, mouse
  • Immunoglobulin G
  • Interleukin-2
  • Interleukin-2 Receptor alpha Subunit
  • Receptors, Fc
  • Recombinant Fusion Proteins