Preconditioning therapy with lentiviral vector-programmed dendritic cells accelerates the homeostatic expansion of antigen-reactive human T cells in NOD.Rag1-/-.IL-2rγc-/- mice.
Preconditioning therapy with lentiviral vector-programmed dendritic cells accelerates the homeostatic expansion of antigen-reactive human T cells in NOD.Rag1-/-.IL-2rγc-/- mice.
复制标题
慢病毒载体编程树突状细胞的预处理治疗可加速 NOD.Rag1-/-.IL-2rγc-/- 小鼠中抗原反应性人类 T 细胞的稳态扩张。
作者：
G. Salguero;B. Sundarasetty;Sylvia Borchers;D. Wedekind;B. Eiz;S. Velaga;Adan Chari Jirmo;G. Behrens;G. Warnecke;Ann‐Kathrin Knöfel;R. Blasczyk;E. Mischak;A. Ganser;R. Stripecke
基于树突状细胞（DC）的免疫是一种有效的策略，直接针对移植后病毒再激活的迅速和持久的免疫应答。在这里，我们表明，过夜慢病毒载体（LV）基因转移到人单核细胞共表达粒细胞-巨噬细胞集落刺激因子和白细胞介素（IL）-4诱导的自分化的DC（SMART-DC）与稳定的DC免疫表型在培养数周，并分泌几种炎性细胞因子。在LV转导后1天皮下注射免疫缺陷NOD.Rag1（-/-）.IL2rγ（-/-）（NRG）小鼠的SMART-DC在体内稳定一个月。比较“常规”DC（cDC）和SMART-DC加速自体人T细胞的扩增、生物分布和抗原刺激的效力。使用从人巨细胞病毒（hCMV）反应性供体获得的外周血细胞和全长hCMV pp 65抗原蛋白或肽。在静脉内输注T细胞之前一周，将负载有pp 65的DC皮下施用到NRG小鼠中作为预处理。光学成像分析表明，在用SMART-DC-pp 65预处理的小鼠中，T细胞直接募集到免疫部位，随后扩散到脾脏和其他器官。在输注后几天内可以观察到人CD 8（+）和CD 4（+）T细胞的急剧扩增，这与针对不同pp 65表位的一致可测量的CD 8（+）效应记忆T细胞应答相关。因此，该小鼠模型证明了SMART-DC加速人淋巴细胞扩增的原理证明，导致针对hCMV-pp 65的多功能和抗原特异性免疫应答。
Dendritic cell (DC)-based immunization is a potent strategy to direct prompt and durable immune responses against viral reactivations after transplantations. Here, we show that overnight lentiviral vector (LV) gene transfer into human monocytes co-expressing granulocyte-macrophage colony stimulating factor and interleukin (IL)-4 induced self-differentiated DCs (SMART-DCs) with stable DC immunophenotype over weeks in culture and secreted several inflammatory cytokines. SMART-DCs injected subcutaneously in immunodeficient NOD.Rag1(-/-).IL2rγ(-/-) (NRG) mice 1 day after LV transduction were stable for a month in vivo. "Conventional" DCs (cDCs) and SMART-DCs were compared with regard to their potency to accelerate the expansion, biodistribution, and antigenic stimulation of autologous human T cells. Peripheral blood cells obtained from human cytomegalovirus (hCMV)-reactive donors and full-length hCMV pp65 antigenic protein or peptides were used. DCs loaded with pp65 were administered subcutaneously into NRG mice as a preconditioning treatment a week prior to intravenous infusion with T cells. Optical imaging analyses demonstrated that in mice preconditioned with SMART-DC-pp65, T cells were directly recruited to the immunization site and subsequently spread to the spleen and other organs. A dramatic expansion of both human CD8(+) and CD4(+) T cells could be observed within a few days after infusion, and this was associated with consistent measurable CD8(+) effector memory T-cell responses against different pp65 epitopes. Thus, this mouse model demonstrates the proof-of-principle for SMART-DCs to accelerate expansion of human lymphocytes, resulting in poly-functional and antigen-specific immune responses against hCMV-pp65.
影响因子：
20.3
作者：
K. Yamashita;U. Choi;Patricia C. Woltz;Susan F. Foster;M. Sneller;F. Hakim;D. Fowler;M. Bishop;S. Pavletic;M. Tamari;K. Castro;A. Barrett;R. Childs;G. Illei;S. Leitman;H. Malech;M. Horwitz
通讯作者：
K. Yamashita;U. Choi;Patricia C. Woltz;Susan F. Foster;M. Sneller;F. Hakim;D. Fowler;M. Bishop;S. Pavletic;M. Tamari;K. Castro;A. Barrett;R. Childs;G. Illei;S. Leitman;H. Malech;M. Horwitz
慢病毒载体介导的小鼠骨髓细胞自主分化为免疫有效的树突状细胞疫苗。
DOI：
10.1038/mt.sj.6300126
发表时间：
2007
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
--
作者：
Koya,RichardC;Kimura,Takahiro;Ribas,Antoni;Rozengurt,Nora;Lawson,GregoryW;Faure-Kumar,Emmanuelle;Wang,He-jing;Herschman,Harvey;Kasahara,Noriyuki;Stripecke,Renata
通讯作者：
Stripecke,Renata