Spatiotemporal in vivo tracking of polyclonal human regulatory T cells reveals a role for innate immune cells in Treg transplant recruitment
Article
Jacob, J., Nadkarni, S., Volpe, A., Peng, Q., Tung, S. L., Hannen, R. F., Mohseni, Y. R., Scotta, C., Marelli-Berg, F. M., Lechler, R. I., Smyth, L., Fruhwirth, G. O. and Lombardi, G. 2020. Spatiotemporal in vivo tracking of polyclonal human regulatory T cells reveals a role for innate immune cells in Treg transplant recruitment. Molecular Therapy - Methods and Clinical Development. 20, pp. 324-336. https://doi.org/10.1016/j.omtm.2020.12.003
Authors | Jacob, J., Nadkarni, S., Volpe, A., Peng, Q., Tung, S. L., Hannen, R. F., Mohseni, Y. R., Scotta, C., Marelli-Berg, F. M., Lechler, R. I., Smyth, L., Fruhwirth, G. O. and Lombardi, G. |
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Abstract | Regulatory T cells (Tregs) are emerging as a new cell-based therapy in solid organ transplantation. Adoptive transfer of Tregs was 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 behaviour, they were subsequently administered to humanized mice with human skin transplants. Traceable Tregs were quantified in skin grafts by non-invasive nanoSPECT/CT for up to 40 days and results 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 thereby addressing a fundamental need in Treg therapy development and offering clinically compatible methodology for future Treg therapy imaging in humans. |
Journal | Molecular Therapy - Methods and Clinical Development |
Journal citation | 20, pp. 324-336 |
ISSN | 2329-0501 |
Year | 2020 |
Publisher | Elsevier (Cell Press) |
Accepted author manuscript | License File Access Level Repository staff only |
Publisher's version | License File Access Level Anyone |
Digital Object Identifier (DOI) | https://doi.org/10.1016/j.omtm.2020.12.003 |
Publication dates | |
Online | 09 Dec 2020 |
Publication process dates | |
Accepted | 02 Dec 2020 |
Deposited | 15 Dec 2020 |
Funder | British Heart Foundation |
Medical Research Council | |
Cancer Research UK | |
Wellcome Trust | |
Engineering and Physical Sciences Research Council | |
National Institute for Health Research | |
Copyright holder | © 2021 The Authors. |
https://repository.uel.ac.uk/item/88w79
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