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
AuthorsJacob, 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.
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.

JournalMolecular Therapy - Methods and Clinical Development
Journal citation20, pp. 324-336
ISSN2329-0501
Year2020
PublisherElsevier (Cell Press)
Accepted author manuscript
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Digital Object Identifier (DOI)https://doi.org/10.1016/j.omtm.2020.12.003
Publication dates
Online09 Dec 2020
Publication process dates
Accepted02 Dec 2020
Deposited15 Dec 2020
FunderBritish 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.
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