CD28 costimulation is essential for human T regulatory expansion and function.
CD28 costimulation is essential for human T regulatory expansion and function.
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DOI：
10.4049/jimmunol.181.4.2855
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发表时间：
2008-08-15
期刊：
影响因子：
--
通讯作者：
Riley JL
中科院分区：
文献类型：
--
作者：
Golovina TN;Mikheeva T;Suhoski MM;Aqui NA;Tai VC;Shan X;Liu R;Balcarcel RR;Fisher N;Levine BL;Carroll RG;Warner N;Blazar BR;June CH;Riley JL
外周血T调节细胞(Tregs)所需的共刺激要求尚不清楚。利用基于细胞的人工APC，我们发现CD28，而不是ICOS，OX40，4-1BB，CD27，或CD40-L共刺激，在体外保持了高水平的Foxp3表达和抑制功能。在免疫缺陷小鼠中，只有在雷帕霉素存在的情况下CD28共刺激持续产生持续抑制异种移植物抗宿主病的Tregs。在雷帕霉素存在的情况下，用CD28共刺激在培养8-12天后重新刺激Tregs，在不到3周的时间内使Tregs扩增1000倍。接下来，我们确定其他共刺激途径是否可以增强CD28共刺激Tregs的复制潜力。我们观察到，当OX40共刺激增强CD28共刺激的Tregs的增殖能力时，Foxp3的表达和抑制功能减弱。这些研究表明，扩增Tregs的共刺激需求不同于T效应细胞，此外，他们扩展了对小鼠Tregs的研究结果，表明人类胸腺后Tregs需要CD28共刺激来扩大和维持体内有效的抑制功能。
The costimulatory requirements required for peripheral blood T regulatory cells (Tregs) are unclear. Using cell-based artificial APCs (aAPC) we found that CD28, but not ICOS, OX40, 4-1BB, CD27, or CD40-L costimulation, maintained high levels of Foxp3 expression and in vitro suppressive function. Only CD28 costimulation in the presence of rapamycin consistently generated Tregs that consistently suppressed xeno-GVHD in immunodeficient mice. Restimulation of Tregs after 8-12 days of culture with CD28 costimulation in the presence of rapamycin resulted in >1000-fold expansion of Tregs in less than 3 weeks. Next, we determined whether other costimulatory pathways could augment the replicative potential of CD28-costimulated Tregs. We observed that while OX40 costimulation augmented the proliferative capacity of CD28-costimulated Tregs, Foxp3 expression and suppressive function were diminished. These studies indicate that the costimulatory requirements to expand Tregs differ from T effector cells, and furthermore, they extend findings from mouse Tregs to demonstratethat human post-thymic Tregs require CD28 costimulation to expand and maintain potent suppressive function in vivo.
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影响因子：
4.4
作者：
Diehl, L;van Mierlo, GJD;Offringa, R
通讯作者：
Offringa, R
DOI：
10.1111/j.1749-6632.2003.tb06052.x
发表时间：
2003-01-01
期刊：
IMMUNE MECHANISMS AND DISEASE
影响因子：
--
作者：
Foell, J;McCausland, M;Mittler, RS
通讯作者：
Mittler, RS
DOI：
10.1084/jem.20042020
发表时间：
2005-01-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
影响因子：
20.3
作者：
Godfrey, WR;Spoden, DJ;Porter, SB
通讯作者：
Porter, SB
影响因子：
15.3
作者：
Herman, AE;Freeman, GJ;Benoist, C
通讯作者：
Benoist, C