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Challenges for labeling and longitudinal tracking of adoptively transferred autoreactive T lymphocytes in an experimental type-1 diabetes model

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Abstract

Objective

Tracking the autoreactive T-cell migration in the pancreatic region after labeling with fluorinated nanoparticles (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[3-(2-pyridyldithio)propionate]-perfluoro-15-crown-5-ether nanoparticles, PDP-PFCE NPs) in a diabetic murine model using 19F MRI.

Materials and methods

Synthesis of novel PDP-PFCE fluorine tracer was performed for in vitro labeling of T cells. Labeling conditions were optimized using different PDP-PFCE NPs concentrations. For in vivo 19F MRI, mice were longitudinally followed after adoptive transfer of activated, autoreactive, labeled T cells in NOD.SCID mice.

Results

Established MR protocols were used for challenging T cell labeling to track inflammation in a model of diabetes after successful labeling of CD4+ and CD8+ T cells with PDP-PFCE NPs. However, T cells were difficult to be detected in vivo after their engraftment in animals.

Discussion

We showed successful in vitro labeling of T cells using novel fluorinated liposomal nanoparticles. However, insufficient and slow accumulation of labeled T cells and subsequent T cell proliferation in the pancreatic region remains as limitations of in vivo cell imaging by 19F MRI.

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Acknowledgements

The authors are grateful for financial support by the European Commission for the FP7 MC-ITN ‘BetaTrain’ (EU-FP7/207-2013/ 289932), by the European ERA-NET project ‘CryptoView’ (3rd call of the FP7 programme Infect-ERA), by the Flemish Wetenschap Onderzoek (FWO) for the projects G.0B28.14 and G.0A75.14, by the Agentschap Innoveren & Ondernemen for the IWT-SBO ‘NanoComit’ (140061).

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Authors and Affiliations

  1. Biomedical MRI/MoSAIC, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium

    Shweta Saini, Bella Manshian & Uwe Himmelreich

  2. Laboratory of Hepatology, CHROMETA Department, KU Leuven, Leuven, Belgium

    Hannelie Korf

  3. Philips Research China, Shanghai, China

    Sayuan Liang

  4. Ghent Research Group on Nanomedicines, Ghent University, Ghent, Belgium

    Rein Verbeke, Koen Raemdonck, Ine Lentacker & Stefaan C. De Smedt

  5. Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium

    Conny Gysemans

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  1. Shweta Saini
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Contributions

Study conception and design: SS, HK, IL, UH. Methodology: SL, HK, RV, KR, CG. Experimentation: SS, HK, BM, RV, SL. Analysis and interpretation of data: SS, HK, BM, UH. Drafting of manuscript: SS. Critical revision: HK, CG, IL, SD, UH.

Corresponding author

Correspondence to Uwe Himmelreich.

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The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors. Experiments involving mice were performed in accordance with regional, national and international standards on animal welfare, in particular the European Union Directive 2010/63/EU, and approved and overseen by the Animal Care and Ethical Committees of the University of Leuven.

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Saini, S., Korf, H., Liang, S. et al. Challenges for labeling and longitudinal tracking of adoptively transferred autoreactive T lymphocytes in an experimental type-1 diabetes model. Magn Reson Mater Phy 32, 295–305 (2019). https://doi.org/10.1007/s10334-018-0720-x

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  • DOI: https://doi.org/10.1007/s10334-018-0720-x

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