Expression of Helios, an Ikaros Transcription Factor Family Member, Differentiates Thymic-Derived from Peripherally Induced Foxp3+ T Regulatory Cells

被引:1050
作者
Thornton, Angela M. [1 ]
Korty, Patricia E. [1 ]
Tran, Dat Q. [1 ]
Wohlfert, Elizabeth A. [2 ]
Murray, Patrick E. [1 ]
Belkaid, Yasmine [2 ]
Shevach, Ethan M. [1 ]
机构
[1] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA
[2] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA
基金
美国国家卫生研究院;
关键词
TGF-BETA; IN-VIVO; GENE; ACTIVATION; GENERATION; INDUCTION; ABSENCE; SELF; LYMPHOCYTES; ENTEROPATHY;
D O I
10.4049/jimmunol.0904028
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Helios, a member of the Ikaros transcription factor family, is preferentially expressed at the mRNA level by regulatory T cells (Treg cells). We evaluated Helios protein expression using a newly generated mAb and demonstrated that it is expressed in all thymocytes at the double negative 2 stage of thymic development. Although Helios was expressed by 100% of CD4(+)CD8(-)Foxp3(+) thymocytes, its expression in peripheral lymphoid tissues was restricted to a subpopulation (similar to 70%) of Foxp3(+) T cells in mice and humans. Neither mouse nor human naive T cells induced to express Foxp3 in vitro by TCR stimulation in the presence of TGF-beta expressed Helios. Ag-specific Foxp3(+) T cells induced in vivo by Ag feeding also failed to express Helios. Collectively, these results demonstrate that Helios is potentially a specific marker of thymic-derived Treg cells and raises the possibility that a significant percentage of Foxp3(+) Treg cells are generated extrathymically. The Journal of Immunology, 2010, 184: 3433-3441.
引用
收藏
页码:3433 / 3441
页数:9
相关论文
共 46 条
[31]   Predominant interaction of both Ikaros and Helios with the NuRD complex in immature thymocytes [J].
Sridharan, Rupa ;
Smale, Stephen T. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (41) :30227-30238
[32]   Distinct subsets of FoxP3+ regulatory T cells participate in the control of immune responses [J].
Stephens, Geoffrey L. ;
Andersson, John ;
Shevach, Ethan M. .
JOURNAL OF IMMUNOLOGY, 2007, 178 (11) :6901-6911
[33]   Foxp3-dependent and -independent molecules specific for CD25+CD4+ natural regulatory T cells revealed by DNA microarray analysis [J].
Sugimoto, Naoshi ;
Oida, Takatoku ;
Hirota, Keiji ;
Nakamura, Kyoko ;
Nomura, Takashi ;
Uchiyama, Takashi ;
Sakaguchi, Shimon .
INTERNATIONAL IMMUNOLOGY, 2006, 18 (08) :1197-1209
[34]   Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid [J].
Sun, Cheng-Ming ;
Hall, Jason A. ;
Blank, Rebecca B. ;
Bouladoux, Nicolas ;
Oukka, Mohamed ;
Mora, J. Rodrigo ;
Belkaid, Yasmine .
JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (08) :1775-1785
[35]   Ikaros enforces the costimulatory requirement for IL2 gene expression and is required for anergy induction in CD4+ T lymphocytes [J].
Thomas, Rajan M. ;
Chunder, Neelanjana ;
Chen, Chunxia ;
Umetsu, Sarah E. ;
Winandy, Susan ;
Wells, Andrew D. .
JOURNAL OF IMMUNOLOGY, 2007, 179 (11) :7305-7315
[36]   Activation requirements for the induction of CD4+CD25+ T cell suppressor function [J].
Thornton, AM ;
Piccirillo, CA ;
Shevach, EM .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2004, 34 (02) :366-376
[37]   Induction of FOXP3 expression in naive human CD4+FOXP3- T cells by T-cell receptor stimulation is transforming growth factor-β-dependent but does not confer a regulatory phenotype [J].
Tran, Dat Q. ;
Ramsey, Heather ;
Shevach, Ethan M. .
BLOOD, 2007, 110 (08) :2983-2990
[38]   Selective defects in the development of the fetal and adult lymphoid system in mice with an Ikaros null mutation [J].
Wang, JH ;
Nichogiannopoulou, A ;
Wu, L ;
Sun, L ;
Sharpe, AH ;
Bigby, M ;
Georgopoulos, K .
IMMUNITY, 1996, 5 (06) :537-549
[39]   Aiolos regulates B cell activation and maturation to effector state [J].
Wang, JH ;
Avitahl, N ;
Cariappa, A ;
Friedrich, C ;
Ikeda, T ;
Renold, A ;
Andrikopoulos, K ;
Liang, LB ;
Pillai, S ;
Morgan, BA ;
Georgopoulos, K .
IMMUNITY, 1998, 9 (04) :543-553
[40]   X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy [J].
Wildin, RS ;
Ramsdell, F ;
Peake, J ;
Faravelli, F ;
Casanova, JL ;
Buist, N ;
Levy-Lahad, E ;
Mazzella, M ;
Goulet, O ;
Perroni, L ;
Bricarelli, FD ;
Byrne, G ;
McEuen, M ;
Proll, S ;
Appleby, M ;
Brunkow, ME .
NATURE GENETICS, 2001, 27 (01) :18-20