Neonatal tolerance revisited again: specific CTL priming in mouse neonates exposed to small numbers of semi- or fully allogeneic spleen cells.
Neonatal tolerance revisited again: specific CTL priming in mouse neonates exposed to small numbers of semi- or fully allogeneic spleen cells.
复制标题
再次回顾新生儿耐受性：暴露于少量半或完全同种异体脾细胞的小鼠新生儿的特异性 CTL 启动。
DOI：
10.1002/eji.200324271
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Levy,RobertB
中科院分区：
文献类型：
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作者：
Adkins,Becky;Jones,Monica;Bu,Yurong;Levy,RobertB
新生小鼠和成年小鼠对同种异体细胞产生不同的反应。给新生儿注射完全同种异体细胞会导致致死性移植物vs。而注射半同种异体（F1）细胞可导致对同种异体抗原的终身耐受，通常以特异性CTL无反应性为标志。相比之下，注射了相同数量的两种细胞类型的成人被激活并产生强烈的抗供体CTL活性。这种差异反应的一种可能是免疫系统的CTL臂发育不成熟。最近的研究表明，新生儿能够建立成熟的CTL反应，但只有在强Th1促进剂存在的情况下。在这里，我们证明了新生儿在暴露于完全或半同种异体脾细胞的情况下，能够产生强烈的MHC I类限制性CTL活性。使用比诱导GVHD或耐受水平低约10倍的细胞剂量产生特异性CTL活性。因此，目前的研究表明，只要供体细胞的剂量足够低，小鼠新生体的异位反应性CTL活性的能力就完全成熟。这些结果对于已知人类胎儿和婴儿暴露于少量母体细胞具有重要意义。
Neonatal and adult mice mount distinct responses to allogeneic cells. Injection of neonates with fully allogeneic cells results in lethal graft‐vs.‐host disease (GVHD), whereas injection of semi‐allogeneic (F1) cells leads to lifelong tolerance to the alloantigens, often marked by specific CTL non‐responsiveness. In contrast, adults injected with the same number of either cell type become primed and develop vigorous anti‐donor CTL activity. One possibility for this differential responsiveness may be developmental immaturity in the CTL arm of the immune system. Recent studies have shown that neonates are capable of mounting mature CTL responses, but only in the presence of strong Th1‐promoting agents. Here, we demonstrate that neonates are competent to develop vigorous MHC class I‐restricted CTL activityin vivoupon exposure to either fully or semi‐allogeneic spleen cells. Specific CTL activity was generated using doses of cells approximately tenfold lower than levels used for the induction of GVHD or tolerance. Thus, the present studies demonstrate that mouse neonates are fully mature in their capacity to develop alloreactive CTL activity, as long as the dose of donor cells is low enough. These results have important implications for the known exposure of human fetuses and infants to small numbers of maternal cells.