Generation of TCR-Expressing Innate Lymphoid-like Helper Cells that Induce Cytotoxic T Cell-Mediated Anti-leukemic Cell Response.
Generation of TCR-Expressing Innate Lymphoid-like Helper Cells that Induce Cytotoxic T Cell-Mediated Anti-leukemic Cell Response.
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DOI：
10.1016/j.stemcr.2018.04.025
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发表时间：
2018-06-05
影响因子：
5.9
通讯作者：
Kaneko S
中科院分区：
文献类型：
--
作者：
Ueda N;Uemura Y;Zhang R;Kitayama S;Iriguchi S;Kawai Y;Yasui Y;Tatsumi M;Ueda T;Liu TY;Mizoro Y;Okada C;Watanabe A;Nakanishi M;Senju S;Nishimura Y;Kuzushima K;Kiyoi H;Naoe T;Kaneko S
CD4+T辅助细胞(Th)活化是诱导细胞毒性T淋巴细胞(CTL)抗肿瘤反应的关键。我们对慢性粒细胞白血病(CML)来源的b3a2多肽的Th克隆进行了重新编程，使其具有多能性，并将其重新分化为原始的表达TCR的T细胞(iPS-T细胞)，其基因表达模式类似于第1组固有淋巴样细胞。CD4基因转导iPS-T细胞通过B3a2多肽特异性TCR增强B3a2多肽特异性应答。IL-2和IL-15刺激iPS-T细胞上调CD40配体(CD40L)的表达。在Wilms Tumor 1(WT1)多肽存在下，由CD4修饰的CD40LHigh iPS-T细胞诱导的抗原特异性树突状细胞(DC)刺激WT1特异性CTL免疫，从而在体内外消除表达WT1多肽的CML细胞。因此，CD40LHigh iPS-T细胞的CD4修饰产生先天类淋巴辅助细胞，诱导BCR-ABL特异性TCR信号，通过DC成熟介导有效的抗白血病CTL应答，显示出抗白血病辅助免疫治疗的潜力。IPSC来源的T细胞与组1先天淋巴样细胞具有分子相似性。IPSC来源的CD40LHigh T细胞佐剂通过DC诱导白血病特异性CTL。Kaneko及其同事描述了CD4+T辅助克隆来源的IPSCs的产生和细胞向T细胞的分化，具有与组1先天淋巴样细胞更一致的分子特征和功能特性。再生细胞的CD4转导和CD40配体的高度纯化以抗原特异性的方式通过树突状细胞增强了抗原特异性佐剂反应。
CD4+ T helper (Th) cell activation is essential for inducing cytotoxic T lymphocyte (CTL) responses against malignancy. We reprogrammed a Th clone specific for chronic myelogenous leukemia (CML)-derived b3a2 peptide to pluripotency and re-differentiated the cells into original TCR-expressing T-lineage cells (iPS-T cells) with gene expression patterns resembling those of group 1 innate lymphoid cells. CD4 gene transduction into iPS-T cells enhanced b3a2 peptide-specific responses via b3a2 peptide-specific TCR. iPS-T cells upregulated CD40 ligand (CD40L) expression in response to interleukin-2 and interleukin-15. In the presence of Wilms tumor 1 (WT1) peptide, antigen-specific dendritic cells (DCs) conditioned by CD4-modified CD40Lhigh iPS-T cells stimulated WT1-specific CTL priming, which eliminated WT1 peptide-expressing CML cells in vitro and in vivo. Thus, CD4 modification of CD40Lhigh iPS-T cells generates innate lymphoid helper-like cells inducing bcr-abl-specific TCR signaling that mediates effectiveanti-leukemic CTL responses via DC maturation, showing potential for adjuvant immunotherapy against leukemia. iPSC-derived T cells have molecular similarity to group 1 innate lymphoid cells iPSC-derived CD40Lhigh T cell-adjuvants induce leukemia-specific CTLs via DCs Kaneko and colleagues describe the generation of CD4+ T helper clone-derived iPSCs and differentiation of the cells into T-lineage cells, which had molecular signatures and functional properties more consistent with group 1 innate lymphoid cells. CD4 transduction and CD40 ligand high population purification of the regenerated cells enhanced the antigen-specific adjuvant responses via dendritic cells in an antigen-specific manner.
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影响因子：
3.7
作者：
Groom JR;Luster AD
通讯作者：
Luster AD
DOI：
10.1084/jem.185.12.2053
发表时间：
1997-06-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Carbone E;Ruggiero G;Terrazzano G;Palomba C;Manzo C;Fontana S;Spits H;Kärre K;Zappacosta S
通讯作者：
Zappacosta S
先天淋巴样细胞会整合基质和免疫信号，从而增强脾脏边缘区B细胞的抗体产生。
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
5.9
作者：
Kitayama S;Zhang R;Liu TY;Ueda N;Iriguchi S;Yasui Y;Kawai Y;Tatsumi M;Hirai N;Mizoro Y;Iwama T;Watanabe A;Nakanishi M;Kuzushima K;Uemura Y;Kaneko S
通讯作者：
Kaneko S
影响因子：
64.8
作者：
Ridge, JP;Di Rosa, F;Matzinger, P
通讯作者：
Matzinger, P