Adoptive transfer of effector CD8+ T cells derived from central memory cells establishes persistent T cell memory in primates
Adoptive transfer of effector CD8+ T cells derived from central memory cells establishes persistent T cell memory in primates
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DOI：
10.1172/jci32103
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发表时间：
2008-01-01
影响因子：
15.9
通讯作者：
Riddell, Stanley R.
中科院分区：
文献类型：
--
作者：
Berger, Carolina;Jensen, Michael C.;Riddell, Stanley R.
抗原特异性T细胞在体外扩增后的过继性转移正被积极用于治疗人类感染和恶性肿瘤。可用于过继免疫治疗的T细胞群包括效应记忆细胞和中枢记忆细胞，它们在表型、功能和归巢方面有所不同。过继性免疫治疗的有效性要求转移的T细胞在体内持续存在，但鉴定通过体外培养进行数值扩增后能够在体内重复存活的T细胞已被证明是困难的。在猕猴中，来自中枢记忆T细胞（而非效应记忆T细胞）的抗原特异性CD8(+) T细胞克隆在体内长期存在，重新获得记忆T细胞的表型和功能特性，并占据记忆T细胞的壁龛。这些结果表明，从中枢记忆T细胞中分离的克隆衍生的CD8(+) T细胞与从效应记忆T细胞中分离的CD8(+) T细胞不同，并且保留了一种内在的能力，使它们能够在过继转移后存活并恢复到记忆细胞池。这些结果可能对选择T细胞扩增或设计用于人类感染或恶性肿瘤的过继免疫治疗具有重要意义。
The adoptive transfer of antigen-specific T cells that have been expanded ex vivo is being actively pursued to treat infections and malignancy in humans. The T cell populations that are available for adoptive immunotherapy include both effector memory and central memory cells, and these differ in phenotype, function, and homing. The efficacy of adoptive immunotherapy requires that transferred T cells persist in vivo, but identifying T cells that can reproducibly survive in vivo after they have been numerically expanded by in vitro culture has proven difficult. Here we show that in macaques, antigen-specific CD8(+) T cell clones derived from central memory T cells, but not effector memory T cells, persisted long-term in vivo, reacquired phenotypic and functional properties of memory T cells, and occupied memory T cell niches. These results demonstrate that clonally derived CD8(+) T cells isolated from central memory T cells are distinct from those derived from effector memory T cells and retain an intrinsic capacity that enables them to survive after adoptive transfer and revert to the memory cell pool. These results could have significant implications for the selection of T cells to expand or to engineer for adoptive immunotherapy of human infections or malignancy.