Tumor Rejection Effects of Allorestricted Tumor Peptide-Specific CD4+ T Cells on Human Cervical Cancer Cell Xenograft in Nude Mice
Tumor Rejection Effects of Allorestricted Tumor Peptide-Specific CD4+ T Cells on Human Cervical Cancer Cell Xenograft in Nude Mice
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同种异体限制性肿瘤肽特异性 CD4 T 细胞对裸鼠人宫颈癌细胞异种移植物的肿瘤排斥作用
DOI：
10.3727/096368912x640510
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发表时间：
2012
影响因子：
3.3
通讯作者：
Xiongwen Wu
中科院分区：
文献类型：
--
作者：
Yinhong Song;Wei Sun;Xiufang Weng;Zhihui Liang;Qian Yu;Zhigang Wang;Lichen Ouyang;Jun Chen;Xiaolin Wu;G. Shen;Xiongwen Wu
肿瘤特异性同种异体反应性CD 4 + T细胞的产生对于避免肿瘤耐受是重要的。在这里，我们产生同种异体限制性肽特异性的CD 4 + T细胞的淋巴细胞和自体单核细胞携带同种异体HLA-DR 15分子与其限制性肽的共培养。二聚体HLA-DR 15/IgG 1-Fc融合蛋白（二聚体）与HLA-DR 15阴性（HLA-DR 15-ve）单核细胞的结合使单核细胞包被同种异体表位。HLA-DR 15-ve淋巴细胞与负载二聚体的自体单核细胞共培养后，CD 4 + T细胞增殖增加，Th 1细胞诱导增加。共培养原液显示特异性二聚体染色的CD 4 + T细胞的频率增加，并且扩增的CD 4 + T细胞显示响应于特异性TCR配体的IFN-γ产生增加。在用同时表达HLA-DR 15和E7抗原的人宫颈癌细胞SiHa攻击的裸鼠中观察通过共培养培养的同种异体限制性E7特异性CD 4 + T细胞的肿瘤排斥作用，因为在过继转移CD 4 + T细胞后，小鼠的肿瘤回避和寿命得到改善。这项研究可能有助于开发将移植物抗白血病或移植物抗肿瘤反应与移植物抗宿主病分开的策略，并增加对肿瘤或病毒抗原特异性的人类高亲和力TCR库。
Generation of tumor specific alloreactive CD4+ T cells is important to circumvent tumor tolerance. Here, we generate allorestricted peptide-specific CD4+ T cells by coculture of lymphocytes and autologous monocytes bearing allogeneic HLA-DR15 molecule associated with its restricted peptide. Binding of a dimeric HLA-DR15/IgG1-Fc fusion protein (the dimer) to HLA-DR15 negative (HLA-DR15-ve) monocytes made the monocytes coated with the allogeneic epitope. An increased proliferation of CD4+ T cells and induction of Th1 cells appeared after coculturing of HLA-DR15-ve lymphocytes and the autologous monocytes loaded with the dimer. The cocultural bulks showed an increased frequency of the specific dimer-stained CD4+ T cells and the expanded CD4+ T cells exhibited an elevated IFN-γ production in response to specific TCR ligand. Tumor rejection effects of the allorestricted E7-specific CD4+ T cells raised by the coculture were observed in nude mice challenged with human cervical cancer cell SiHa expressing both HLA-DR15 and E7 antigens, as the tumor avoidance and life span of the mice were improved after adoptive transfer of the CD4+ T cells. This study may help to develop strategies to separate graft-versus-leukemia or graft-versus-tumor reaction from graft-versus-host disease, and add to the pool of human high-avidity TCRs specific for tumor or virus antigens.
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I 类限制性同种反应性细胞毒性 T 淋巴细胞可识别一系列复杂的特定 MHC 相关肽。
DOI：
--
发表时间：
1998
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Wang,W;Man,S;Gulden,PH;Hunt,DF;Engelhard,VH
通讯作者：
Engelhard,VH
影响因子：
3.8
作者：
KAUR, P;MCDOUGALL, JK;CONE, R
通讯作者：
CONE, R
影响因子：
4.4
作者：
MAN, S;SALTER, RD;ENGELHARD, VH
通讯作者：
ENGELHARD, VH
影响因子：
20.3
作者：
Johnson, Laura A.;Morgan, Richard A.;Rosenberg, Steven A.
通讯作者：
Rosenberg, Steven A.
非溶细胞性 CD4(+) T 细胞群对心脏同种异体移植物的急性排斥。
影响因子：
6.2
作者：
VanBuskirk,AM;Wakely,ME;Orosz,CG
通讯作者：
Orosz,CG