CD25 Appears Non Essential for Human Peripheral Treg Maintenance In Vivo

被引:25
作者
de Herve, Marie-Ghislaine de Goer [1 ,2 ,3 ]
Gonzales, Emmanuel [4 ,5 ]
Hendel-Chavez, Houria [1 ,2 ]
Decline, Jean-Luc [4 ,5 ]
Mourier, Olivia [4 ,5 ]
Abbed, Karim [1 ]
Jacquemin, Emmanuel [4 ,5 ]
Taoufik, Yassine [1 ,2 ,3 ]
机构
[1] CHU Bicetre, Unite Immunol Biol, Le Kremlin Bicetre, France
[2] INSERM 10 12, Fac Med, Le Kremlin Bicetre, France
[3] Univ Paris Sud, Fac Med, F-94275 Le Kremlin Bicetre, France
[4] CHU Bicetre, Serv Hepatol Pediat, Le Kremlin Bicetre, France
[5] CHU Bicetre, Ctr Reference Natl Atresie Voies Biliaires, Le Kremlin Bicetre, France
关键词
FOOD ALLERGY; LIVER-TRANSPLANTATION; STRUCTURAL BASIS; CELLS; INTERLEUKIN-2; TACROLIMUS; EXPRESSION; FOXP3; BASILIXIMAB; CHILDREN;
D O I
10.1371/journal.pone.0011784
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
Background: IL-2 has been reported to be critical for peripheral T-reg survival in mouse models. Here, we examined T-reg maintenance in a series of paediatric liver transplant recipients who received basiliximab, a therapeutic anti-CD25 monoclonal antibody. Methodology/Principal Findings: FoxP3(+) CD4 T cells were analyzed by flow cytometry before liver grafting and more than 9 months later. We found that in vivo CD25 blockade did not lead to Treg depletion: the proportion of FoxP3(+) cells among CD4 T cells and the level of FoxP3 expression were both unchanged. IL-2R beta expression was enhanced in FoxP3(+) cells both before and after basiliximab treatment, while the level of IL-2R gamma expression was similar in T-regs and non-T-regs. No significant change in the weak or absent expression of IL-7R alpha and IL-15R alpha expression on FoxP3(+) cells was observed. Although the proportion of FoxP3(+) cells among CD4 T cells did not vary, food allergies occurred more rapidly after liver grafting in patients who received basiliximab, raising questions as to T-reg functionality in vivo in the absence of functional CD25. Conclusions: CD25 appears non essential for human T-reg peripheral maintenance in vivo. However, our results raise questions as to T-reg functionality after therapeutic CD25 targeting.
引用
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页码:1 / 5
页数:5
相关论文
共 37 条
[1]   Immune tolerance in allergy [J].
Akdis, Muebeccel .
CURRENT OPINION IN IMMUNOLOGY, 2009, 21 (06) :700-707
[2]   Essential role for STAT5 signaling in CD25+CD4+ regulatory T cell homeostasis and the maintenance of self-tolerance [J].
Antov, A ;
Yang, L ;
Vig, M ;
Baltimore, D ;
Van Parijs, L .
JOURNAL OF IMMUNOLOGY, 2003, 171 (07) :3435-3441
[3]   Allergic disease after pediatric liver transplantation with systemic tacrolimus and cyclosporine a therapy [J].
Arikan, C ;
Kilic, M ;
Tokat, Y ;
Aydogdu, S .
TRANSPLANTATION PROCEEDINGS, 2003, 35 (08) :3039-3041
[4]   A function for IL-7R for CD4+CD25+Foxp3+ T regulatory cells [J].
Bayer, Allison L. ;
Lee, Joon Youb ;
de la Barrera, Anabel ;
Surh, Charles D. ;
Malek, Thomas R. .
JOURNAL OF IMMUNOLOGY, 2008, 181 (01) :225-234
[5]   Natural regulatory T cells in infectious disease [J].
Belkaid, Y ;
Rouse, BT .
NATURE IMMUNOLOGY, 2005, 6 (04) :353-360
[6]   Identification of their epitope reveals the structural basis for the mechanism of action of the immunosuppressive antibodies basiliximab and daclizumab [J].
Binder, Mascha ;
Voegtle, Friederike-Nora ;
Michelfelder, Stefan ;
Mueller, Fabian ;
Illerhaus, Gerald ;
Sundararajan, Sangeeth ;
Mertelsmann, Roland ;
Trepel, Martin .
CANCER RESEARCH, 2007, 67 (08) :3518-3523
[7]   The effect of costimulatory and interleukin 2 receptor blockade on regulatory T cells in renal transplantation [J].
Bluestone, J. A. ;
Liu, W. ;
Yabu, J. M. ;
Laszik, Z. G. ;
Putnam, A. ;
Belingheri, M. ;
Gross, D. M. ;
Townsend, R. M. ;
Vincenti, F. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2008, 8 (10) :2086-2096
[8]   The development of food allergy after liver transplantation [J].
Boyle, RJ ;
Hardikar, W ;
Tang, MLK .
LIVER TRANSPLANTATION, 2005, 11 (03) :326-330
[9]   THE INTERLEUKIN-2 T-CELL SYSTEM - A NEW CELL-GROWTH MODEL [J].
CANTRELL, DA ;
SMITH, KA .
SCIENCE, 1984, 224 (4655) :1312-1316
[10]   Development and function of agonist-induced CD25+Foxp3+ regulatory T cells in the absence of interleukin 2 signaling [J].
D'Cruz, LM ;
Klein, L .
NATURE IMMUNOLOGY, 2005, 6 (11) :1152-1159