Spatiotemporal in vivo tracking of polyclonal human regulatory T cells (Tregs) reveals a role for innate immune cells in Treg transplant recruitment.
Spatiotemporal in vivo tracking of polyclonal human regulatory T cells (Tregs) reveals a role for innate immune cells in Treg transplant recruitment.
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多克隆人调节性T细胞（Tcells）的时空体内追踪揭示了先天免疫细胞在Treg移植募集中的作用。
DOI：
10.1016/j.omtm.2020.12.003
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发表时间：
2021-03-12
期刊：
影响因子：
--
通讯作者：
Lombardi G
中科院分区：
文献类型：
--
作者：
Jacob J;Nadkarni S;Volpe A;Peng Q;Tung SL;Hannen RF;Mohseni YR;Scotta C;Marelli-Berg FM;Lechler RI;Smyth LA;Fruhwirth GO;Lombardi G
调节性T细胞（Regulatory T cells，TCFs）是近年来在实体器官移植中出现的一种新的细胞治疗方法。临床前已显示Treg的连续转移可防止移植物排斥，并且Treg疗法的安全性已在临床试验中得到证实。尽管取得了这些成功，但过继转移的TdR的体内分布和持久性仍然难以捉摸，这阻碍了临床转化。在这里，我们使用GMP兼容的协议和慢病毒转导他们与人类钠碘同向转运体，使他们在体内可追踪的放射性核素成像分离人类THBE。对工程化的人TCLs的表型、存活、抑制能力和报告基因功能进行表征。为了研究它们的贩运行为，随后将它们施用给具有人类皮肤移植的人源化小鼠。通过非侵入性纳米单光子发射计算机断层扫描（nanoSPECT）/计算机断层扫描（CT）对皮肤移植物中的可追踪THBG进行定量长达40天，并对结果进行体外验证。使用这种方法，我们证明了Treg向皮肤移植物的运输受到受体Gr-1+先天免疫细胞的存在的调节。我们证明了放射性核素报告基因提供的定量Treg体内跟踪的实用性，解决了Treg治疗开发的基本需求，并为人类未来的Treg治疗成像提供了临床兼容的方法。连续调节性T细胞（Treg）疗法作为器官移植中的治疗出现，但Treg在体内的分布和持久性仍然是难以捉摸的。Jacob等人开发了一种非侵入性长期Treg治疗跟踪方法，并在移植的人源化模型中验证了该方法。适应未来的临床Treg治疗成像是简单的。
Regulatory T cells (Tregs) are emerging as a new cell-based therapy in solid organ transplantation. Adoptive transfer of Tregs has been shown preclinically to protect from graft rejection, and the safety of Treg therapy has been demonstrated in clinical trials. Despite these successes, the in vivo distribution and persistence of adoptively transferred Tregs remained elusive, which hampers clinical translation. Here we isolated human Tregs using a GMP-compatible protocol and lentivirally transduced them with the human sodium iodide symporter to render them traceable in vivo by radionuclide imaging. Engineered human Tregs were characterized for phenotype, survival, suppressive capacity, and reporter function. To study their trafficking behavior, they were subsequently administered to humanized mice with human skin transplants. Traceable Tregs were quantified in skin grafts by non-invasive nano-single-photon emission computed tomography (nanoSPECT)/computed tomography (CT) for up to 40 days, and the results were validated ex vivo. Using this approach, we demonstrated that Treg trafficking to skin grafts was regulated by the presence of recipient Gr-1+ innate immune cells. We demonstrated the utility of radionuclide reporter gene-afforded quantitative Treg in vivo tracking, addressing a fundamental need in Treg therapy development and offering a clinically compatible methodology for future Treg therapy imaging in humans. Adoptive regulatory T cell (Treg) therapy emerges as a treatment in organ transplantation, but Treg in vivo distribution and persistence remain elusive. Jacob et al. developed a non-invasive long-term Treg therapy tracking method and validated it in humanized models of transplantation. Adaption for future clinical Treg therapy imaging is straightforward.
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DOI：
10.1084/jem.194.6.847
发表时间：
2001-09-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Iellem A;Mariani M;Lang R;Recalde H;Panina-Bordignon P;Sinigaglia F;D'Ambrosio D
通讯作者：
D'Ambrosio D
影响因子：
9.3
作者：
Fruhwirth, Gilbert O.;Diocou, Seckou;Mullen, Greg E. D.
通讯作者：
Mullen, Greg E. D.
影响因子：
4.6
作者：
Diocou, S.;Volpe, A.;Fruhwirth, G. O.
通讯作者：
Fruhwirth, G. O.
影响因子：
6.1
作者：
Krystufkova, Eva;Sekerkova, Alena;Viklicky, Ondrej
通讯作者：
Viklicky, Ondrej
DOI：
10.1073/pnas.0707207104
发表时间：
2007-12-18
影响因子：
11.1
作者：
Dohan, Orsolya;Portulano, Carla;Carrasco, Nancy
通讯作者：
Carrasco, Nancy