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

共 46 条

[21] CYTOKINE-BINDING PROTEINS - STIMULATING ANTAGONISTS [J].

KLEIN, B ;

BRAILLY, H .

IMMUNOLOGY TODAY, 1995, 16 (05) :216-220

[22] B and T lymphocyte attenuator regulates CD8+ T cell-intrinsic homeostasis and memory cell generation [J].

Krieg, Carsten ;

Boyman, Onur ;

Fu, Yang-Xin ;

Kaye, Jonathan .

NATURE IMMUNOLOGY, 2007, 8 (02) :162-171

[23] IL-2-and CD25-dependent immunoregulatory mechanisms in the homeostasis of T-cell subsets [J].

Letourneau, Sven ;

Krieg, Carsten ;

Pantaleo, Giuseppe ;

Boyman, Onur .

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2009, 123 (04) :758-762

[24] The biology of interleukin-2 [J].

Matek, Thomas R. .

ANNUAL REVIEW OF IMMUNOLOGY, 2008, 26 :453-479

[25] IL-7 TRANSGENIC MICE - ANALYSIS OF THE ROLE OF IL-7 IN THE DIFFERENTIATION OF THYMOCYTES IN-VIVO AND IN-VITRO [J].

MERTSCHING, E ;

BURDET, C ;

CEREDIG, R .

INTERNATIONAL IMMUNOLOGY, 1995, 7 (03) :401-414

[26] THE IL-2 RECEPTOR COMPLEX - ITS STRUCTURE, FUNCTION, AND TARGET GENES [J].

MINAMI, Y ;

KONO, T ;

MIYAZAKI, T ;

TANIGUCHI, T .

ANNUAL REVIEW OF IMMUNOLOGY, 1993, 11 :245-268

[27] Cutting Edge: IL-2 Immune Complexes As a Therapy for Persistent Virus Infection [J].

Molloy, Michael J. ;

Zhang, Weijun ;

Usherwood, Edward J. .

JOURNAL OF IMMUNOLOGY, 2009, 182 (08) :4512-4515

[28] IL-2/anti-IL-2 antibody complex enhances vaccine-mediated antigen-specific CD8+ T cell responses and increases the ratio of effector/memory CD8+ T cells to regulatory T cells [J].

Mostboeck, Sven ;

Lutsiak, M. E. Christine ;

Milenic, Diane E. ;

Baidoo, Kwamena ;

Schlom, Jeffrey ;

Sabzevari, Helen .

JOURNAL OF IMMUNOLOGY, 2008, 180 (07) :5118-5129

[29] HETERODIMERIZATION OF THE IL-2 RECEPTOR BETA-CHAIN AND GAMMA-CHAIN CYTOPLASMIC DOMAINS IS REQUIRED FOR SIGNALING [J].

NAKAMURA, Y ;

RUSSELL, SM ;

MESS, SA ;

FRIEDMANN, M ;

ERDOS, M ;

FRANCOIS, C ;

JACQUES, Y ;

ADELSTEIN, S ;

LEONARD, WJ .

NATURE, 1994, 369 (6478) :330-333

[30] CD4+ CD25+ Foxp3+ regulatory T cells induce cytokine deprivation -mediated apoptosis of effector CD4+ T cells [J].

Pandiyan, Pushpa ;

Zheng, Lixin ;

Ishihara, Satoru ;

Reed, Jennifer ;

Lenardo, Michael J. .

NATURE IMMUNOLOGY, 2007, 8 (12) :1353-1362

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