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

被引：171

作者：

Letourneau, Sven ^{[1
]}

van Leeuwen, Ester M. M. ^{[2
]}

Krieg, Carsten ^{[1
]}

Martin, Chris ^{[2
]}

Pantaleo, Giuseppe ^{[1
,3
]}

Sprent, Jonathan ^{[4
,5
,6
]}

Surh, Charles D. ^{[2
,5
]}

Boyman, Onur ^{[1
]}

机构：

[1] Univ Lausanne Hosp, Div Immunol & Allergy, CH-1011 Lausanne, Switzerland

[2] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA

[3] Univ Lausanne Hosp, Swiss Vaccine Res Inst, CH-1011 Lausanne, Switzerland

[4] Garvan Inst Med Res, Darlinghurst, NSW 2010, Australia

[5] World Class Univ, Integrat Biosci & Biotechnol Program, Pohang, South Korea

[6] Univ New S Wales, St Vincents Clin Sch, Sydney, NSW 2010, Australia

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 05期

基金：

瑞士国家科学基金会;

关键词：

CD25; cytokine; cytokine/mAb complexes; T cell homeostasis; Fc receptor; CD8(+) T-CELLS; IN-VIVO; CUTTING EDGE; IMMUNE-COMPLEXES; HEPARAN-SULFATE; DEFICIENT MICE; FUSION PROTEIN; BETA-CHAIN; INTERLEUKIN-2; HOMEOSTASIS;

D O I：

10.1073/pnas.0909384107

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：2171 / 2176

页数：6

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