Molecular and functional characterization of allogantigen-specific anergic T cells suitable for cell therapy
Molecular and functional characterization of allogantigen-specific anergic T cells suitable for cell therapy
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DOI：
10.3324/haematol.2010.025825
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发表时间：
2010-12-01
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影响因子：
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通讯作者：
Roncarolo, Maria Grazia
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文献类型：
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作者：
Bacchetta, Rosa;Gregori, Silvia;Roncarolo, Maria Grazia
背景CD 4（+）调节性T细胞是一种特异性的T细胞亚群，具有主动控制免疫应答的功能。几个实验协议已被用来扩大自然调节T细胞和产生自适应1型调节T细胞的调节T细胞为基础的therapeutilization.Design和MethodsThe外源性重组人白细胞介素-10诱导同种抗原特异性无能的T细胞的能力进行了研究，并比较了来自致耐受性树突状细胞的白细胞介素-10，在混合淋巴细胞培养。所得到的anergized T细胞的效应功能的详细表征reported.ResultsInterleukin-10，无论是外源性的或来自致耐受性树突状细胞，诱导一个人口的同种抗原特异性T细胞（白细胞介素-10-anergized T细胞）含有1型调节T细胞，这是无能和积极抑制同种抗原特异性效应T细胞内存在的混合人口。白细胞介素-10诱导的无反应性是转化生长因子-β非依赖性的，并且与同种异体抗原特异性细胞毒性T淋巴细胞前体的频率降低相关，但是白细胞介素-10无反应性T细胞仍然对第三方、细菌和病毒抗原有反应。致耐受性树突状细胞在产生1型调节性T细胞前体方面比外源性白细胞介素-10更强大，并且在HLA匹配的供体中也是有效的。我们已经开发了一种有效的和可重复的体外方法来产生抗原特异性的1型调节性T-细胞前体，其以最少的细胞操作从总外周血细胞开始，并且适于产生用于基于调节性T细胞的疗法的1型调节性T细胞。
BackgroundCD4(+) regulatory T cells are a specialized subset of T cells that actively control immune responses. Several experimental protocols have been used to expand natural regulatory T cells and to generate adaptive type 1 regulatory T cells for regulatory T-cell-based therapies.Design and MethodsThe ability of exogenous recombinant human interleukin-10 to induce alloantigen-specific anergy in T cells was investigated and compared to that of interleukin-10 derived from tolerogenic dendritic cells, in mixed lymphocyte cultures. A detailed characterization of the effector functions of the resulting anergized T cells is reported.ResultsInterleukin-10, whether exogenous or derived from tolerogenic dendritic cells, induces a population of alloantigen-specific T cells (interleukin-10-anergized T cells) containing type 1 regulatory T cells, which are anergic and actively suppress alloantigen-specific effector T cells present within the mixed population. Interleukin-10-induced anergy is transforming growth factor-beta independent, and is associated with a decreased frequency of alloantigen-specific cytotoxic T lymphocyte precursors, but interleukin-10-anergized T cells are still responsive to third-party, bacterial, and viral antigens. Tolerogenic dendritic cells are more powerful than exogenous interleukin-10 in generating type 1 regulatory T-cell precursors, and are also effective in the context of HLA-matched donors.Conclusions Based on these studies, we have developed an efficient and reproducible in vitro method to generate antigen-specific type 1 regulatory T-cell precursors starting from total peripheral blood cells with minimal cell manipulation and suitable for generating type 1 regulatory T cells for regulatory T-cell-based therapies.