IL-7 is superior to IL-2 for ex vivo expansion of tumour-specific CD4+ T cells
IL-7 is superior to IL-2 for ex vivo expansion of tumour-specific CD4+ T cells
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DOI：
10.1002/eji.200939801
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发表时间：
2010-02-01
影响因子：
5.4
通讯作者：
Mondino, Anna
中科院分区：
文献类型：
--
作者：
Caserta, Stefano;Alessi, Patrizia;Mondino, Anna
众所周知，肿瘤会阻碍自然和疫苗诱导的肿瘤特异性CD4(+)T细胞反应。过继T细胞治疗有可能避免功能性耐受，增强抗肿瘤保护反应。虽然目前已有适合扩增细胞毒性CD8(+)T细胞的方案，但有关肿瘤特异性的CD4(+)T细胞的数据仍然很少。我们在这里报道，在体内，CD4(+)T细胞对肿瘤相关的Ag敏感，在体外对IL-7做出反应而增殖，不需要外源性Ag刺激，并在保留记忆样表型的同时积累数倍。细胞增殖和存活都是IL-7暴露后肿瘤敏感型T细胞和其他记忆细胞和幼稚淋巴细胞生长的原因。此外，IL-2，以前用于扩大抗肿瘤的CTL，促进肿瘤特异性的CD4(+)T细胞的积累。然而，在体外和体内，IL-7在保持淋巴细胞活性方面优于IL-2，保持了辅助性CD4(+)T细胞在移植到荷瘤宿主后赋予治疗效果所需的那些特性。总之，我们的数据支持IL-7在提取适合过继T细胞治疗的记忆样CD4(+)T细胞方面的独特作用。
It is well established that tumours hinder both natural and vaccine-induced tumour-specific CD4(+) T-cell responses. Adoptive T-cell therapy has the potential to circumvent functional tolerance and enhance anti-tumour protective responses. While protocols suitable for the expansion of cytotoxic CD8(+) T cells are currently available, data on tumour-specific CD4(+) T cells remain scarce. We report here that CD4(+) T cells sensitized to tumour-associated Ag in vivo, proliferate in vitro in response to IL-7 without the need for exogenous Ag stimulation and accumulate several folds while preserving a memory-like phenotype. Both cell proliferation and survival accounts for the outgrowth of tumour-sensitized T cells among other memory and naive lymphocytes following exposure to IL-7. Also IL-2, previously used to expand anti-tumour CTL, promotes tumour-specific CD4(+) T-cell accumulation. However, IL-7 is superior to IL-2 at preserving lymphocyte viability, in vitro and in vivo, maintaining those properties, that are required by helper CD4(+) T cells to confer therapeutic efficacy upon transplantation in tumour-bearing hosts. Together our data support a unique role for IL-7 in retrieving memory-like CD4(+) T cells suitable for adoptive T-cell therapy.