Substrate-bound CCL21 and ICAM1 combined with soluble IL-6 collectively augment the expansion of antigen-specific murine CD4+ T cells
Substrate-bound CCL21 and ICAM1 combined with soluble IL-6 collectively augment the expansion of antigen-specific murine CD4+ T cells
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DOI：
10.1182/bloodadvances.2016001545
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发表时间：
2017-06-01
期刊：
影响因子：
7.5
通讯作者：
Friedman, Nir
中科院分区：
文献类型：
--
作者：
Adutler-Lieber, Shimrit;Zaretsky, Irina;Friedman, Nir
淋巴结复杂微环境中的免疫过程涉及多种细胞间、细胞-基质和旁分泌相互作用，导致抗原特异性T细胞的扩增。受淋巴结微环境的启发，我们的目标是开发一种离体的“合成免疫小生境”（SIN），它可以有效地刺激抗原激活的CD 4（+）T细胞的增殖。这种工程化的SIN由涂覆有趋化因子C-C基序配体21（CCL 21）和细胞间粘附分子1（ICAM 1）的表面组成，所述表面与添加到培养基中的可溶性细胞因子白细胞介素6（IL-6）偶联。当被负载卵白蛋白的树突状细胞激活时，在常规未涂覆的培养板上生长的OT-II T细胞在树突状细胞周围形成非粘附的动态簇。我们发现，功能化的板表面与CCL 21和ICAM 1和IL-6的培养基中的添加显着增加T细胞增殖和转化的培养拓扑结构从悬浮的三维细胞簇成一个坚定的，基板附着的单层细胞。我们的研究结果表明，这种SIN的组分共同调节T细胞相互作用，并以抗原特异性方式增强T细胞的增殖和存活，可能作为一种强大的方法来扩增免疫调节性T细胞。
Immune processes within the complex microenvironment of the lymph node involve multiple intercellular, cell-matrix, and paracrine interactions, resulting in the expansion of antigen-specific T cells. Inspired by the lymph node microenvironment, we aimed to develop an ex vivo "synthetic immune niche" (SIN), which could effectively stimulate the proliferation of antigen-activated CD4(+) T cells. This engineered SIN consisted of surfaces coated with the chemokine C-C motif ligand 21 (CCL21) and with the intercellular adhesion molecule 1 (ICAM1), coupled with the soluble cytokine interleukin 6 (IL-6) added to the culture medium. When activated by ovalbumin-loaded dendritic cells, OT-II T cells growing on regular uncoated culture plates form nonadherent, dynamic clusters around the dendritic cells. We found that functionalization of the plate surface with CCL21 and ICAM1 and the addition of IL-6 to the medium dramatically increases T-cell proliferation and transforms the culture topology from that of suspended 3-dimensional cell clusters into a firm, substrate-attached monolayer of cells. Our findings demonstrate that the components of this SIN collectively modulate T-cell interactions and augment both the proliferation and survival of T cells in an antigen-specific manner, potentially serving as a powerful approach for expanding immunotherapeutic T cells.