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PMID: 20133862 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 107 ·No. 5 ·2010-02-02 ·Pages 2171-6

Létourneau S, van Leeuwen EM, Krieg C, Martin C, Pantaleo G, Sprent J, Surh CD, Boyman O

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.

MeSH Terms
Animals Antibodies, Blocking/administration & dosage Antigen-Antibody Complex/metabolism Half-Life Homeostasis Immunoglobulin G/metabolism Interleukin-2/immunology,metabolism Interleukin-2 Receptor alpha Subunit/antagonists & inhibitors,deficiency,genetics,metabolism Mice Mice, Congenic Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Receptors, Fc/metabolism Recombinant Fusion Proteins/immunology,metabolism
Chemicals
Antibodies, Blocking Antigen-Antibody Complex Il2ra protein, mouse Immunoglobulin G Interleukin-2 Interleukin-2 Receptor alpha Subunit Receptors, Fc Recombinant Fusion Proteins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Létourneau Sven
Division of Immunology and Allergy, University Hospital of Lausanne, CH-1011 Lausanne, Switzerland.
van Leeuwen Ester M M
Krieg Carsten
Martin Chris
Pantaleo Giuseppe
Sprent Jonathan
Surh Charles D
Boyman Onur
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.0909384107
Published
2010-02-02
Epub
2010-00-19
Pages
2171-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2836659
Subset
IM
Grants
NIAID NIH HHS · R21 AI090610 · United States
External Links
PubMed source DOI: 10.1073/pnas.0909384107 PMC Full Text View journal details
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