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

Abstract

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.

Type Journal
ISBN 1091-6490 (Electronic) 0027-8424 (Linking)
Authors Letourneau, S.; van Leeuwen, E. M.; Krieg, C.; Martin, C.; Pantaleo, G.; Sprent, J.; Surh, C. D.; Boyman, O.;
Publisher Name PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Published Date 2010-01-01
Published Volume 107
Published Issue 5
Published Pages 2171-6
Status Published in-print
URL link to publisher's version http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20133862
OpenAccess link to author's accepted manuscript version https://publications.gimr.garvan.org.au/open-access/10579