Effector differentiation is not prerequisite for generation of memory cytotoxic T lymphocytes
Effector differentiation is not prerequisite for generation of memory cytotoxic T lymphocytes
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DOI：
10.1172/jci200113296
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发表时间：
2001-09-01
影响因子：
15.9
通讯作者：
von Andrian, UH
中科院分区：
文献类型：
--
作者：
Manjunath, N;Shankar, P;von Andrian, UH
短寿命效应T细胞和长寿命记忆细胞之间的谱系关系尚未完全了解。我们之前已经描述了T-GFP小鼠，其中幼稚和早期活化的T细胞均匀地表达GFP，而已经分化为效应细胞毒性T细胞的细胞选择性地失去GFP表达。在这里，我们研究了抗原特异性的CD 8 T细胞分化使用T GFP小鼠杂交TCR转基因（Tg）小鼠P14（特异性的淋巴细胞性脉络丛脑膜炎病毒糖蛋白肽，gp 33 -41）。在用抗原肽活化后，在高剂量IL-2中培养的P14 XT-GFP CD 8（+）T细胞发育成具有效应表型和功能的细胞：它们是类胚细胞，失去GFP表达，表达高水平的活化和效应标志物，并且能够立即发挥细胞毒性功能。相反，在IL-15或低剂量IL-2中培养的细胞从未发育成成熟的效应细胞。相反，它们类似于记忆细胞：它们更小，是GFP（+），不表达效应标记物，并且不能立即产生细胞毒性。然而，它们在体外介导快速回忆反应。过继转移后，它们在体内存活至少10周，并在抗原再激发后产生与内源性产生的记忆细胞一样有效的二次免疫应答。除了提供一种简单的方法来产生几乎无限数量的记忆细胞，我们的研究结果表明，效应分化不是记忆细胞产生的先决条件。
The lineage relationship between short-lived effector T cells and long-lived memory cells is not fully understood. We have described T-GFP mice previously, in which naive and early activated T cells express GFP uniformly, whereas cells that have differentiated into effector cytotoxic T cells selectively lose GFP expression. Here we studied antigen-specific CD8 T cell differentiation using T GFP mice crossed to the TCR transgenic (Tg) mice P14 (specific for the lymphocytic choriomeningitis virus glycoprotein peptide, gp33-41). After activation with antigenic peptide, P14XT-GFP CD8(+) T cells cultured in high-dose IL-2 developed into cells with effector phenotype and function: they were blastoid, lost GFP expression, expressed high levels of activation and effector markers, and were capable of immediate cytotoxic function. In contrast, cells cultured in IL-15 or low-dose IL-2 never developed into full-fledged effector cells. Rather, they resembled memory cells: they were smaller, were GFP(+), did not express effector markers, and were incapable of immediate cytotoxicity. However, they mediated rapid-recall responses in vitro. After adoptive transfer, they survived in vivo for at least 10 weeks and mounted a secondary immune response after antigen rechallenge that was as potent as endogenously generated memory cells. In addition to providing a simple means to generate memory cells in virtually unlimited numbers, our results suggest that effector differentiation is not a prerequisite for memory cell generation.