Human natural killer T cells are heterogeneous in their capacity to reprogram their effector functions.
Human natural killer T cells are heterogeneous in their capacity to reprogram their effector functions.
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DOI：
10.1371/journal.pone.0000050
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发表时间：
2006-12-20
期刊：
影响因子：
3.7
通讯作者：
Unutmaz D
中科院分区：
文献类型：
--
作者：
Eger KA;Sundrud MS;Motsinger AA;Tseng M;Van Kaer L;Unutmaz D
自然杀伤T（NKT）细胞是T细胞的一个子集，有助于增强和调节免疫反应。虽然已经鉴定出具有不同效应子功能的人NKT细胞亚群，但尚不清楚这些亚群的效应子功能是否在发育期间被印记或可以在外周中选择性地重编程。我们发现，新生儿NKT细胞主要是CD 4+，并表达更高水平的CCR 7和CD 62 L和更低水平的CD 94和CD 161比成人CD 4+或CD 4 − NKT细胞亚群。因此，新生儿NKT细胞比成人CD 4 + NKT细胞更灵活的能力，获得Th 1-或Th 2-样的功能，无论是在姜黄素介导的极化或异位表达的Th 1或Th 2转录因子T-bet和加塔-3，分别。与其更分化的表型一致，CD 4- NKT细胞主要对功能性重编程具有抗性，并显示出更高的细胞毒性功能。与常规T细胞相反，新生儿NKT细胞的CXCR 3表达和细胞毒性能力都不能被重编程。总之，这些结果表明，新生儿CD 4+、成人CD 4+和成人CD 4 − NKT可能代表了独特的成熟状态，人类NKT细胞的某些功能可能是发育印记的，而其他功能则是在外周成熟和分化过程中获得的，类似于传统的T细胞亚群。鉴于NKT细胞强大的免疫调节功能，这些发现对开发新的基于NKT细胞的疗法和疫苗具有重要意义。
Natural killer T (NKT) cells are a subset of T cells that help potentiate and regulate immune responses. Although human NKT cell subsets with distinct effector functions have been identified, it is unclear whether the effector functions of these subsets are imprinted during development or can be selectively reprogrammed in the periphery. We found that neonatal NKT cells are predominantly CD4+ and express higher levels of CCR7 and CD62L and lower levels of CD94 and CD161 than adult CD4+ or CD4− NKT cell subsets. Accordingly, neonatal NKT cells were more flexible than adult CD4+ NKT cells in their capacity to acquire Th1- or Th2-like functions upon either cytokine-mediated polarization or ectopic expression of the Th1 or Th2 transcription factors T-bet and GATA-3, respectively. Consistent with their more differentiated phenotype, CD4- NKT cells were predominantly resistant to functional reprogramming and displayed higher cytotoxic function. In contrast to conventional T cells, neither the expression of CXCR3 nor the cytotoxic capacity of neonatal NKT cells could be reprogrammed. Together, these results suggest that neonatal CD4+, adult CD4+, and adult CD4− NKT may represent unique states of maturation and that some functions of human NKT cells may be developmentally imprinted, while others are acquired similar to conventional T cell subsets during peripheral maturation and differentiation. Given the potent immuno-regulatory functions of NKT cells, these findings have important implications for the development of novel NKT cell-based therapeutics and vaccines.
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影响因子：
20.3
作者：
Kim, CH;Johnston, B;Butcher, EC
通讯作者：
Butcher, EC
影响因子：
4.4
作者：
EMOTO, M;EMOTO, Y;KAUFMANN, SHE
通讯作者：
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作者：
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DOI：
10.1084/jem.20011786
发表时间：
2002-03-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
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通讯作者：
Brenner MB
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影响因子：
15.3
作者：
Lee, Peter T;Benlagha, Kamel;Teyton, Luc;Bendelac, Albert
通讯作者：
Bendelac, Albert