Role of CD47 in the induction of human naive T cell anergy
Role of CD47 in the induction of human naive T cell anergy
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DOI：
10.4049/jimmunol.167.5.2459
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发表时间：
2001-09-01
影响因子：
4.4
通讯作者：
Sarfati, M
中科院分区：
文献类型：
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作者：
Avice, MN;Rubio, M;Sarfati, M
我们最近报道了CD47结扎抑制在IL-12而非IL-4存在下激活的脐带血单个核细胞释放IL-2，从而阻止IL-12R β(2)表达的诱导和Th1的获得，而不是Th2表型的获得。在缺乏外源性细胞因子的情况下，脐带血单个核细胞的CD47结扎可促进低反应性T细胞的发育。初始细胞用CD47 mAb处理3天，在IL-2中扩增9-12天，然后用CD3和CD28共结合重新刺激。在这些条件下产生的效应T细胞被认为是无能的，因为它们在单细胞水平上产生的IL-2数量减少，并且表现出1)增殖能力受损，2)分泌Th1/Th2细胞因子的能力受损，以及3)对IL-2， IL-4或IL-12的反应能力受损。此外，CD47 mAb强烈抑制原代培养中IL-2的产生和IL-2R α的表达以及活化的幼稚T细胞的IL-2反应。CD47 mAb诱导的能量与IL-10无关，而在启动时包含IL-2和IL-4，而不是IL-7，完全恢复T细胞的激活。此外，CD28共刺激阻止了能量的诱导。因此，CD47可能是诱导能量和防止不希望的Th0/Th1反应的潜在靶标，如移植物抗宿主病、同种异体移植物排斥或自身免疫性疾病。
We recently reported that CD47 ligation inhibited IL-2 release by umbilical cord blood mononuclear cells activated in the presence of IL-12, but not IL-4, preventing the induction of IL-12R beta (2) expression and the acquisition of Th1, but not the Th2 phenotype. Here we show that in the absence of exogenous cytokine at priming, CD47 ligation of umbilical cord blood mononuclear cells promotes the development of hyporesponsive T cells. Naive cells were treated with CD47 mAb for 3 days, expanded in IL-2 for 9-12 days, and restimulated by CD3 and CD28 coengagement. Effector T cells generated under these conditions were considered to be anergic because they produced a reduced amount of IL-2 at the single-cell level and displayed an impaired capacity 1) to proliferate, 2) to secrete Th1/Th2 cytokines, and 3) to respond to IL-2, IL-4, or IL-12. Moreover, CD47 mAb strongly suppressed IL-2 production and IL-2R alpha expression in primary cultures and IL-2 response of activated naive T cells. Induction of anergy by CD47 mAb was IL-10 independent, whereas inclusion of IL-2 and IL-4, but not IL-7, at priming fully restored T cell activation. Furthermore, CD28 costimulation prevented induction of anergy. Thus, CD47 may represent a potential target to induce anergy and prevent undesired Th0/Th1 responses such as graft vs host diseases, allograft rejection, or autoimmune diseases.