Tumor-primed, in vitro-activated CD4+ effector T cells establish long-term memory without exogenous cytokine support or ongoing antigen exposure.
Tumor-primed, in vitro-activated CD4+ effector T cells establish long-term memory without exogenous cytokine support or ongoing antigen exposure.
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DOI：
10.4049/jimmunol.0903549
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发表时间：
2010-05-15
期刊：
影响因子：
--
通讯作者：
Plautz GE
中科院分区：
文献类型：
--
作者：
Wang LX;Plautz GE
肿瘤反应性T细胞可以在体内引发，然后在体外活化以提供效应表型和功能的数值扩增和均匀获得。效应T细胞的连续转移介导动物模型中已建立肿瘤的完全消退。一些实验模型表明，T细胞的广泛体外增殖抑制功效，并且TCM提供比TEM更大的活性。临床研究还表明，过继转移的T细胞的持久性与治疗反应相关，因此鉴定使效应细胞数量最大化但保留记忆功能的条件是重要的。在这里，我们证明，过继转移的体外活化效应CD4+ T细胞到无肿瘤同源小鼠介导的排斥肿瘤的挑战9个月后，在这个时候T细胞重新表达活化标志物，并在肿瘤部位进行快速增殖。过继转移后淋巴组织中记忆细胞表型的分析显示高CD44表达和CD62L的异质性表达，表明TEM和TCM表型的混合物。根据CD62L表达水平将记忆细胞分为两个亚群，然后在体外活化。尽管TEM细胞增殖更快，但TEM和TCM细胞都获得了效应子表型和功能。这些数据表明，用于过继免疫治疗的肿瘤反应性T细胞的受控体外扩增也提供了胜任的记忆应答。
Tumor-reactive T cells can be primed in vivo, then activated in vitro to provide numerical expansion and uniform acquisition of effector phenotype and function. Adoptive transfer of effector T cells mediates complete regression of established tumors in animal models. Some experimental models indicate that extensive in vitro proliferation of T cells inhibits efficacy and that TCM provide greater activity than TEM. Clinical studies also demonstrate that persistence of adoptively transferred T cells is associated with therapeutic response, thus identifying conditions to maximize effector cell numbers yet retain memory function are important. Here, we demonstrate that adoptive transfer of in vitro activated effector CD4+ T cells into tumor-free congenic mice mediates rejection of tumor challenge nine months later, at which time T cells re-express activation markers and undergo rapid proliferation at tumor sites. Analysis of the phenotype of memory cells in lymphoid tissues following adoptive transfer shows high CD44 expression with heterogeneous expression of CD62L, indicating a mixture of TEM and TCM phenotypes. Memory cells were sorted into two subsets based on CD62L expression levels and then activated in vitro. Although TEM cells proliferated more rapidly, both TEM and TCM cells acquired effector phenotype and function. These data indicate that controlled in vitro expansion of tumor-reactive T cells for adoptive immunotherapy also provides a competent memory response.
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影响因子：
15.9
作者：
Berger, Carolina;Jensen, Michael C.;Riddell, Stanley R.
通讯作者：
Riddell, Stanley R.
DOI：
10.1073/pnas.0503726102
发表时间：
2005-07-05
影响因子：
11.1
作者：
Klebanoff, CA;Gattinoni, L;Restifo, NP
通讯作者：
Restifo, NP
影响因子：
3.9
作者：
Huang, JP;Khong, HT;Robbins, PF
通讯作者：
Robbins, PF
DOI：
10.1084/jem.20042521
发表时间：
2005-05-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Obst R;van Santen HM;Mathis D;Benoist C
通讯作者：
Benoist C
影响因子：
64.8
作者：
Araki, Koichi;Turner, Alexandra P.;Shaffer, Virginia Oliva;Gangappa, Shivaprakash;Keller, Susanne A.;Bachmann, Martin F.;Larsen, Christian P.;Ahmed, Rafi
通讯作者：
Ahmed, Rafi