2B4 (CD244) induced by selective CD28 blockade functionally regulates allograft-specific CD8+ T cell responses.
2B4 (CD244) induced by selective CD28 blockade functionally regulates allograft-specific CD8+ T cell responses.
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DOI：
10.1084/jem.20130902
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发表时间：
2014-02-10
期刊：
影响因子：
--
通讯作者：
Ford ML
中科院分区：
文献类型：
--
作者：
Liu D;Krummey SM;Badell IR;Wagener M;Schneeweis LA;Stetsko DK;Suchard SJ;Nadler SG;Ford ML
阻断CD28信号导致2B4在初级CD8+效应器上上调，并在控制抗原特异性CD8+T细胞应答中起关键作用。在自身免疫和慢性病毒感染的模型中，越来越多的证据表明，T细胞激活的结果受到细胞表面表达的共刺激和共抑制受体的严重影响。在这里，我们确定了共抑制SLAM家族成员2B4(CD244)在选择性阻断CD28的免疫调节存在的情况下，在减弱初级抗原特异性CD8+T细胞反应中的关键作用。我们的结果显示，在CD28信号被阻断的动物中，2B4对抗原特异性CD8+T细胞具有特异性的上调作用。然而，在CTLA-4Ig(Abatacept)或CD28阻断加抗CTLA-4单抗的动物中，未观察到2B4上调。2B4中抗原特异性CD8+T细胞缺失时，CD28阻断的抑制作用减弱，CD28阻断后B4表达上调在功能上具有显著意义。相反，2B4缺乏对CD8+T细胞在未经修饰的排斥反应或在CTLA-4Ig存在的情况下的反应没有影响。我们的结论是，在保留CTLA-4信号的情况下阻断CD28信号导致2B4在初级CD8+效应器上的独特上调，并且这种2B4表达在控制抗原特异性CD8+T细胞反应中起着关键的功能作用。
Blockade of CD28 signals results in the up-regulation of 2B4 on primary CD8+ effectors and plays a critical role in controlling antigen-specific CD8+ T cell responses. Mounting evidence in models of both autoimmunity and chronic viral infection suggests that the outcome of T cell activation is critically impacted by the constellation of co-stimulatory and co-inhibitory receptors expressed on the cell surface. Here, we identified a critical role for the co-inhibitory SLAM family member 2B4 (CD244) in attenuating primary antigen-specific CD8+ T cell responses in the presence of immune modulation with selective CD28 blockade. Our results reveal a specific up-regulation of 2B4 on antigen-specific CD8+ T cells in animals in which CD28 signaling was blocked. However, 2B4 up-regulation was not observed in animals treated with CTLA-4 Ig (abatacept) or CD28 blockade in the presence of anti–CTLA-4 mAb. 2B4 up-regulation after CD28 blockade was functionally significant, as the inhibitory impact of CD28 blockade was diminished when antigen-specific CD8+ T cells were deficient in 2B4. In contrast, 2B4 deficiency had no effect on CD8+ T cell responses during unmodified rejection or in the presence of CTLA-4 Ig. We conclude that blockade of CD28 signals in the presence of preserved CTLA-4 signals results in the unique up-regulation of 2B4 on primary CD8+ effectors, and that this 2B4 expression plays a critical functional role in controlling antigen-specific CD8+ T cell responses.
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DOI：
10.1111/j.1600-6143.2008.02460.x
发表时间：
2009-01
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Schenk AD;Gorbacheva V;Rabant M;Fairchild RL;Valujskikh A
通讯作者：
Valujskikh A
影响因子：
8.8
作者：
Vincenti, F.;Charpentier, B.;Larsen, C. P.
通讯作者：
Larsen, C. P.
影响因子：
4.6
作者：
Kim, J. R.;Mathew, S. O.;Mathew, P. A.
通讯作者：
Mathew, P. A.
影响因子：
17.1
作者：
Poirier, Nicolas;Azimzadeh, Agnes M.;Vanhove, Bernard
通讯作者：
Vanhove, Bernard
影响因子：
30.5
作者：
Blackburn, Shawn D.;Shin, Haina;Haining, W. Nicholas;Zou, Tao;Workman, Creg J.;Polley, Antonio;Betts, Michael R.;Freeman, Gordon J.;Vignali, Dario A. A.;Wherry, E. John
通讯作者：
Wherry, E. John