KLF13 sustains thymic memory-like CD8(+) T cells in BALB/c mice by regulating IL-4-generating invariant natural killer T cells.

KLF13 sustains thymic memory-like CD8(+) T cells in BALB/c mice by regulating IL-4-generating invariant natural killer T cells.
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DOI:
10.1084/jem.20101527
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发表时间:
2011-05-09
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Krensky AM
Krensky AM
中科院分区:
其他
文献类型:
--
作者:
Lai D;Zhu J;Wang T;Hu-Li J;Terabe M;Berzofsky JA;Clayberger C;Krensky AM

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转录因子KLF 13调节BALB/c与C57 BL/6胸腺中iNKT细胞数量的增加,导致产生足够水平的IL-4以产生记忆样CD 8 + T细胞。“记忆样T细胞”是胸腺细胞的亚群,其通过成熟过程而不是与特异性抗原相互作用获得效应子功能。编码T细胞信号传导蛋白或转录因子的基因的破坏提供了对此类细胞分化的见解。在这项研究中,我们发现,在BALB/c,但不是C57 BL/6,小鼠,胸腺CD 4-CD 8 + T细胞的大部分表现出记忆样表型。在BALB/c小鼠中,由不变的自然杀伤T(iNKT)细胞分泌的IL-4对于记忆样T细胞的产生是必需的且足够的。在C57 BL/6小鼠中,iNKT细胞不太丰富,产生的IL-4不足以诱导胸腺记忆样CD 8 + T细胞。转录因子Kruppel样因子(KLF)13缺陷的BALB/c小鼠具有与C57 BL/6小鼠相当数量的iNKT细胞和极低水平的胸腺记忆样CD 8 + T细胞。这项工作记录了少量KLF 13依赖性iNKT细胞对记忆样CD 8 + T细胞产生的影响。
Transcription factor KLF13 regulates the elevated numbers of iNKT cells in the BALB/c versus C57BL/6 thymus that results in production of sufficient levels of IL-4 to generate memory-like CD8+ T cells. “Memory-like T cells” are a subset of thymic cells that acquire effector function through the maturation process rather than interaction with specific antigen. Disruption of genes encoding T cell signaling proteins or transcription factors have provided insights into the differentiation of such cells. In this study, we show that in BALB/c, but not C57BL/6, mice, a large portion of thymic CD4-CD8+ T cells exhibit a memory-like phenotype. In BALB/c mice, IL-4 secreted by invariant natural killer T (iNKT) cells is both essential and sufficient for the generation of memory-like T cells. In C57BL/6 mice, iNKT cells are less abundant, producing IL-4 that is insufficient to induce thymic memory-like CD8+ T cells. BALB/c mice deficient in the transcription factor Kruppel-like factor (KLF) 13 have comparable numbers of iNKT cells to C57BL/6 mice and extremely low levels of thymic memory-like CD8+ T cells. This work documents the impact of a small number of KLF13-dependent iNKT cells on the generation of memory-like CD8+ T cells.
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