Radiolabelling of Polyclonally Expanded Human Regulatory T Cells (Treg) with ⁸⁹Zr-oxine for Medium-Term In Vivo Cell Tracking
Article
Jacob, J., Volpe, A., Peng, Q., Lechler, R. I., Smyth, L. A., Lombardi, G. and Fruhwirth, G. O. 2023. Radiolabelling of Polyclonally Expanded Human Regulatory T Cells (Treg) with ⁸⁹Zr-oxine for Medium-Term In Vivo Cell Tracking. Molecules. 28 (Art. 1482). https://doi.org/10.3390/molecules28031482
| Authors | Jacob, J., Volpe, A., Peng, Q., Lechler, R. I., Smyth, L. A., Lombardi, G. and Fruhwirth, G. O. |
|---|---|
| Abstract | Regulatory T cells (Tregs) are a promising candidate cell therapy to treat autoimmune diseases and aid the longevity of transplanted solid organs. Despite increasing numbers of clinical trials using human Treg therapy, important questions pertaining to their in vivo fate, distribution, and function remain unanswered. Treg accumulation in relevant tissues was found to be crucial for Treg therapy efficacy, but existing blood-borne biomarkers are unlikely to accurately reflect the tissue state. Non-invasive Treg tracking by whole-body imaging is a promising alternative and can be achieved by direct radiolabelling of Tregs and following the radiolabelled cells with positron emission tomography (PET). Our goal was to evaluate the radiolabelling of polyclonal Tregs with ⁸⁹Zr to permit their in vivo tracking by PET/CT for longer than one week with current preclinical PET instrumentation. We used [⁸⁹Zr]Zr(oxinate)₄ as the cell-labelling agent and achieved successful radiolabelling efficiency of human Tregs spanning 0.1–11.1 Bq ⁸⁹Zr/Treg cell, which would be compatible with PET tracking beyond one week. We characterized the ⁸⁹Zr-Tregs, assessing their phenotypes, and found that they were not tolerating these intracellular ⁸⁹Zr amounts, as they failed to survive or expand in a ⁸⁹Zr-dose-dependent manner. Even at 0.1 Bq ⁸⁹Zr per Treg cell, while ⁸⁹Zr-Tregs remained functional as determined by a five-day-long effector T cell suppression assay, they failed to expand beyond day 3 in vitro. Moreover, PET imaging revealed signs of ⁸⁹Zr-Treg death after adoptive transfer in vivo. In summary, ⁸⁹Zr labelling of Tregs at intracellular radioisotope amounts compatible with cell tracking over several weeks did not achieve the desired outcomes, as ⁸⁹Zr-Tregs failed to expand and survive. Consequently, we conclude that indirect Treg labelling is likely to be the most effective alternative method to satisfy the requirements of this cell tracking scenario. |
| Journal | Molecules |
| Journal citation | 28 (Art. 1482) |
| ISSN | 1420-3049 |
| Year | 2023 |
| Publisher | MDPI |
| Publisher's version | License File Access Level Anyone |
| Digital Object Identifier (DOI) | https://doi.org/10.3390/molecules28031482 |
| Publication dates | |
| Online | 03 Feb 2023 |
| Publication process dates | |
| Accepted | 31 Jan 2023 |
| Deposited | 13 Feb 2023 |
| Copyright holder | © 2023 The Authors |
Permalink -
https://repository.uel.ac.uk/item/8v9y3
Download files
115
total views63
total downloads2
views this month2
downloads this month
Export as
Related outputs
Inhibition of thrombin on endothelium enhances recruitment of regulatory T cells during IRI and when combined with adoptive Treg transfer, significantly protects against acute tissue injury and prolongs allograft survival
Peng, Q., Nowocin, A., Ratnasothy, K., Smith, R. A., Smyth, L., Lechler, R. I., Dorling, A. and Lombardi, G. 2023. Inhibition of thrombin on endothelium enhances recruitment of regulatory T cells during IRI and when combined with adoptive Treg transfer, significantly protects against acute tissue injury and prolongs allograft survival. Frontiers in Immunology. 13 (Art. 980462). https://doi.org/10.3389/fimmu.2022.980462Editorial: Characterisation, functions and roles of antigen-specific regulatory T cells in health and disease
Tran,G. T., Verma, N. D., Smyth, L. and Hall, B. M. 2022. Editorial: Characterisation, functions and roles of antigen-specific regulatory T cells in health and disease. Frontiers in Immunology. 13. https://doi.org/10.3389/fimmu.2022.1022813Nox2-deficient Tregs improve heart transplant outcomes via their increased graft recruitment and enhanced potency
Trevelin, S. C., Zampetaki, A., Sawyer, G., Ivetic, A., Brewer, A. C., Smyth, L. A., Marelli-Berg, F., Köchl, R., Lechler, R. I., Shah, A. M. and Lombardi, G. 2021. Nox2-deficient Tregs improve heart transplant outcomes via their increased graft recruitment and enhanced potency. JCI Insight. 6 (Art. e149301). https://doi.org/10.1172/jci.insight.149301Spatiotemporal in vivo tracking of polyclonal human regulatory T cells reveals a role for innate immune cells in Treg transplant recruitment
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.2020.12.003B lymphocytes contribute to indirect pathway T cell sensitisation via acquisition of extracellular vesicles
Becker, P. D., Ratnasothy, K., Sen, M., Peng, Q., Romano, M., Bazoer, J., Suvitra, E., Stout, A., Hylton, S. G., Dorling, A., Lechler, R. I., Smyth, L. and Lombardi, G. 2020. B lymphocytes contribute to indirect pathway T cell sensitisation via acquisition of extracellular vesicles. American Journal of Transplantation. 21 (4), pp. 1415-1426. https://doi.org/10.1111/ajt.16088Regulatory T Cell Extracellular Vesicles Modify T-Effector Cell Cytokine Production and Protect Against Human Skin Allograft Damage
Tung, S. L., Fanelli, G., Matthews, R. I., Bazoer, J., Letizia, M., Vizcay-Barrena, G., Faruqu, F. N., Philippeos, C., Hannen, R., Al-Jamal, K. T., Smyth, L. and Lombardi, G. 2020. Regulatory T Cell Extracellular Vesicles Modify T-Effector Cell Cytokine Production and Protect Against Human Skin Allograft Damage. Frontiers in Cell and Developmental Biology. 8 (Art. 317). https://doi.org/10.3389/fcell.2020.00317Application of carbon nanotubes in cancer vaccines: Achievements, challenges and chances
Hassan, Hatem A.F.M., Diebold, Sandra S., Smyth, L., Walters, Adam A., Lombardi, Giovanna and Al-Jamal, Khuloud T. 2019. Application of carbon nanotubes in cancer vaccines: Achievements, challenges and chances. Journal of Controlled Release. 297, pp. 79-90. https://doi.org/10.1016/j.jconrel.2019.01.017Protease Activated Receptor 4 as a Novel Modulator of Regulatory T Cell Function
Peng, Q., Ratnasothy, K., Boardman, D. A., Jacob, J., Tung, S. T., McCluskey, D., Smyth, L., Lechler, R. I., Dorling, A. and Lombardi, G. 2019. Protease Activated Receptor 4 as a Novel Modulator of Regulatory T Cell Function. Frontiers in Immunology. 10 (Art. 1311). https://doi.org/10.3389/fimmu.2019.01311Membrane radiolabelling of exosomes for comparative biodistribution analysis in immunocompetent and immunodeficient mice – a novel and universal approach
Faruqu, Farid N., Wang, Julie Tzu-Wen, Xu, Lizhou, McNickle, Luke, Chong, Eden Ming-Yiu, Walters, Adam, Gurney, Mark, Clayton, Aled, Smyth, L., Hider, Robert, Sosabowski, Jane and Al-Jamal, Khuloud T. 2019. Membrane radiolabelling of exosomes for comparative biodistribution analysis in immunocompetent and immunodeficient mice – a novel and universal approach. Theranostics. 9 (6), pp. 1666-1682. https://doi.org/10.7150/thno.27891Nox2 in regulatory T cells promotes angiotensin II–induced cardiovascular remodeling
Emmerson, Amber, Trevelin, Silvia Cellone, Mongue-Din, Heloise, Becker, Pablo D., Ortiz, Carla, Smyth, L., Peng, Qi, Elgueta, Raul, Sawyer, Greta, Ivetic, Aleksandar, Lechler, Robert I., Lombardi, Giovanna and Shah, Ajay M. 2018. Nox2 in regulatory T cells promotes angiotensin II–induced cardiovascular remodeling. Journal of Clinical Investigation. 128 (7), pp. 3088-3101. https://doi.org/10.1172/JCI97490Regulatory T cell-derived extracellular vesicles modify dendritic cell function
Tung, Sim L., Boardman, Dominic A., Sen, Monica, Letizia, Marilena, Peng, Qi, Cianci, Nicole, Dioni, Laura, Carlin, Leo M., Lechler, Robert, Bollati, Valentina, Lombardi, Giovanna and Smyth, L. 2018. Regulatory T cell-derived extracellular vesicles modify dendritic cell function. Scientific Reports. 8, p. 6065. https://doi.org/10.1038/s41598-018-24531-8Galectin-1 is required for the regulatory function of B cells
Alhabbab, R., Blair, P., Smyth, L., Ratnasothy, K., Peng, Q., Moreau, A., Lechler, R., Elgueta, R. and Lombardi, G. 2018. Galectin-1 is required for the regulatory function of B cells. Scientific Reports. 8 (2725). https://doi.org/10.1038/s41598-018-19965-zConstitutive expression of the anti-apoptotic Bcl-2 family member A1 in murine endothelial cells leads to transplant tolerance
Smyth, L., Meader, Lucy, Xiao, Fang, Woodward, Martin, Brady, Hugh J., Lechler, Robert and Lombardi, Giovanna 2017. Constitutive expression of the anti-apoptotic Bcl-2 family member A1 in murine endothelial cells leads to transplant tolerance. Clinical and Experimental Immunology. 188 (2), pp. 219-225. https://doi.org/10.1111/cei.12931Dual stimulation of antigen presenting cells using carbon nanotube-based vaccine delivery system for cancer immunotherapy
Hassan, Hatem A.F.M., Smyth, L., Wang, Julie T.-W., Costa, Pedro M., Ratnasothy, Kulachelvy, Diebold, Sandra S., Lombardi, Giovanna and Al-Jamal, Khuloud T. 2016. Dual stimulation of antigen presenting cells using carbon nanotube-based vaccine delivery system for cancer immunotherapy. Biomaterials. 104, pp. 310-322. https://doi.org/10.1016/j.biomaterials.2016.07.005Regulatory T Cell-Derived Exosomes: Possible Therapeutic and Diagnostic Tools in Transplantation
Agarwal, Akansha, Fanelli, Giorgia, Letizia, Marilena, Tung, Sim Lai, Boardman, Dominic, Lechler, Robert, Lombardi, Giovanna and Smyth, L. 2014. Regulatory T Cell-Derived Exosomes: Possible Therapeutic and Diagnostic Tools in Transplantation. Frontiers in Immunology. 5.UK–Russia Researcher Links Workshop: extracellular vesicles – mechanisms of biogenesis and roles in disease pathogenesis, M.V. Lomonosov Moscow State University, Moscow, Russia, 1–5 March 2015
Kapustin, Alexander N., Kalinina, Natalia, Lopatina, Tatiana, Davidson, Sean M., Iraci, Nunzio, Tamkovich, Svetlana, Smyth, L., Ter-Ovanesyan, Dmitry, Evtushenko, Evgeniy G., Savelieva, Olga, Bertazzo, Sergio, Aushev, Vassiliy, Dragovic, Rebecca, Gracia, Tannia, Heck, Margarete, Parfyonova, Yelena V., Shanahan, Catherine M. and Tkachuk, Vsevolod 2015. UK–Russia Researcher Links Workshop: extracellular vesicles – mechanisms of biogenesis and roles in disease pathogenesis, M.V. Lomonosov Moscow State University, Moscow, Russia, 1–5 March 2015. Journal of Extracellular Vesicles. 4 (1), p. 28094. https://doi.org/10.3402/jev.v4.28094Diversity of gut microflora is required for the generation of B cell with regulatory properties in a skin graft model
Alhabbab, R., Blair, P., Elgueta, R., Stolarczyk, E., Marks, E., Becker, P. D., Ratnasothy, K., Smyth, L., Safinia, N., Sharif-Paghaleh, E., O’Connell, S., Noelle, R. J., Lord, G. M., Howard, J. K., Spencer, J., Lechler, R. I. and Lombardi, G. 2015. Diversity of gut microflora is required for the generation of B cell with regulatory properties in a skin graft model. Scientific Reports. 5, p. 11554.Carbon nanotubes' surface chemistry determines their potency as vaccine nanocarriers in vitro and in vivo
Hassan, Hatem A.F.M., Smyth, L., Rubio, Noelia, Ratnasothy, Kulachelvy, Wang, Julie T.-W., Bansal, Sukhvinder S., Summers, Huw D., Diebold, Sandra S., Lombardi, Giovanna and Al-Jamal, Khuloud T. 2016. Carbon nanotubes' surface chemistry determines their potency as vaccine nanocarriers in vitro and in vivo. Journal of Controlled Release. 225, pp. 205-216. https://doi.org/10.1016/j.jconrel.2016.01.030Continuous acquisition of MHC:peptide complexes by recipient cells contributes to the generation of anti-graft CD8+T cell immunity
Smyth, L., Lechler, Robert I and Lombardi, Giovanna 2016. Continuous acquisition of MHC:peptide complexes by recipient cells contributes to the generation of anti-graft CD8+T cell immunity. American Journal of Transplantation. 17 (1), pp. 60-68. https://doi.org/10.1111/ajt.13996What Is Direct Allorecognition?
Boardman, Dominic A., Jacob, Jacinta, Smyth, L., Lombardi, Giovanna and Lechler, Robert I. 2016. What Is Direct Allorecognition? Current Transplantation Reports. 3 (4), pp. 275-283. https://doi.org/10.1007/s40472-016-0115-8Treg therapy in transplantation a general overview
Romano, Marco, Tung, Sim Lai, Smyth, L. and Lombardi, Giovanna 2016. Treg therapy in transplantation a general overview. Transplant International. 30 (8), pp. 745-753. https://doi.org/10.1111/tri.12909