In vitro generation of CD4+CD25+regulatory cells from murine naive T cells

被引:129
作者
Fantini, Massimo C. [2 ]
Dominitzki, Sabine [1 ]
Rizzo, Angelo [2 ]
Neurath, Markus F. [1 ]
Becker, Christoph [1 ]
机构
[1] Johannes Gutenberg Univ Mainz, Immunol Lab, I Med Clin, D-55131 Mainz, Germany
[2] Johannes Gutenberg Univ Mainz, Immunol Lab, I Med Clin, D-55131 Mainz, Germany
关键词
D O I
10.1038/nprot.2007.258
中图分类号
Q5 [生物化学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
CD4+CD25+ regulatory T cells (Tregs) are crucial for the maintenance of immunological tolerance. Recent data indicate that Tregs not only develop in the thymus during ontogeny but can also differentiate from naive T cells in the periphery. The following protocol describes a method by which Tregs are generated in vitro by stimulation of naive T cells in the presence of transforming growth factor beta (Ti-Tregs). In vitro-induced regulatory T cells express markers of conventional Treg such as CD25 and the genetic program committing transcription factor FoxP3. Functionally the in vitro-generated Ti-Tregs suppress T-cell activation and proliferation while in vivo these cells have been proven to control inflammation in different animal models, suggesting a potential use of these cells for immunotherapy. The protocol can be completed within 5 days.
引用
收藏
页码:1789 / 1794
页数:6
相关论文
共 15 条
[1]
Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation [J].
Asano, M ;
Toda, M ;
Sakaguchi, N ;
Sakaguchi, S .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 184 (02) :387-396
[2]
The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3 [J].
Bennett, CL ;
Christie, J ;
Ramsdell, F ;
Brunkow, ME ;
Ferguson, PJ ;
Whitesell, L ;
Kelly, TE ;
Saulsbury, FT ;
Chance, PF ;
Ochs, HD .
NATURE GENETICS, 2001, 27 (01) :20-21
[3]
Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells [J].
Bettelli, E ;
Carrier, YJ ;
Gao, WD ;
Korn, T ;
Strom, TB ;
Oukka, M ;
Weiner, HL ;
Kuchroo, VK .
NATURE, 2006, 441 (7090) :235-238
[4]
Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-β induction of transcription factor Foxp3 [J].
Chen, WJ ;
Jin, WW ;
Hardegen, N ;
Lei, KJ ;
Li, L ;
Marinos, N ;
McGrady, G ;
Wahl, SM .
JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 198 (12) :1875-1886
[5]
Cutting edge:: IL-2 is essential for TGF-β-mediated induction of Foxp3+ T regulatory cells [J].
Davidson, Todd S. ;
DiPaolo, Richard J. ;
Andersson, John ;
Shevach, Ethan M. .
JOURNAL OF IMMUNOLOGY, 2007, 178 (07) :4022-4026
[6]
Transforming growth factor β induced FoxP3+ regulatory T cells suppress Th1 mediated experimental colitis [J].
Fantini, MC ;
Becker, C ;
Tubbe, I ;
Nikolaev, A ;
Lehr, HA ;
Galle, P ;
Neurath, MF .
GUT, 2006, 55 (05) :671-680
[7]
Cutting edge:: TGF-β induces a regulatory phenotype in CD4+CD25- T cells through Foxp3 induction and down-regulation of Smad7 [J].
Fantini, MC ;
Becker, C ;
Monteleone, G ;
Pallone, F ;
Galle, PR ;
Neurath, MF .
JOURNAL OF IMMUNOLOGY, 2004, 172 (09) :5149-5153
[8]
GODFREY VL, 1991, AM J PATHOL, V138, P1379
[9]
Control of regulatory T cell development by the transcription factor Foxp3 [J].
Hori, S ;
Nomura, T ;
Sakaguchi, S .
SCIENCE, 2003, 299 (5609) :1057-1061
[10]
Cutting edge:: CD4+CD25+ regulatory T cells suppress antigen-specific autoreactive immune responses and central nervous system inflammation during active experimental autoimmune encephalomyelitis [J].
Kohm, AP ;
Carpentier, PA ;
Anger, HA ;
Miller, SD .
JOURNAL OF IMMUNOLOGY, 2002, 169 (09) :4712-4716