Letter | Published:

GFP-specific CD8 T cells enable targeted cell depletion and visualization of T-cell interactions

Nature Biotechnology volume 33, pages 12871292 (2015) | Download Citation

Abstract

There are numerous cell types with scarcely understood functions, whose interactions with the immune system are not well characterized. To facilitate their study, we generated a mouse bearing enhanced green fluorescent protein (EGFP)-specific CD8+ T cells. Transfer of the T cells into EGFP reporter animals can be used to kill EGFP-expressing cells, allowing selective depletion of desired cell types, or to interrogate T-cell interactions with specific populations. Using this system, we eliminate a rare EGFP-expressing cell type in the heart and demonstrate its role in cardiac function. We also show that naive T cells are recruited into the mouse brain by antigen-expressing microglia, providing evidence of an immune surveillance pathway in the central nervous system. The just EGFP death-inducing (Jedi) T cells enable visualization of a T-cell antigen. They also make it possible to utilize hundreds of existing EGFP-expressing mice, tumors, pathogens and other tools, to study T-cell interactions with many different cell types, to model disease states and to determine the functions of poorly characterized cell populations.

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Acknowledgements

We thank A. Annoni, L. Sherman, J. Brody, J. Lafaille, S. Lira, J. Blander and M. Feldmann for helpful discussions. We also thank K. Kelly and the Mouse Genetics and Mouse Targeting facility, and A. Rahman and the Flow Cytometry Core for technical assistance. B.D.B. and M.M. were supported by US National Institutes of Health (NIH) R01AI104848 and R01AI113221. B.D.B. was also supported by a Pilot Award from the Diabetes Research, Obesity and Metabolism Institute and an Innovation Award from the Juvenile Diabetes Research Foundation (JDRF). Y.Z. was supported by NIH1R01HL107376. J.A. was supported by the Robin Chemers Neustein Award, and a JDRF postdoctoral fellowship. V.K. was supported by a Swiss National Foundation Early Postdoc Mobility fellowship.

Author information

Affiliations

  1. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

    • Judith Agudo
    • , Albert Ruzo
    • , Eun Sook Park
    • , Robert Sweeney
    • , Meng Wu
    • , Yong Zhao
    •  & Brian D Brown
  2. Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

    • Veronika Kana
    •  & Miriam Merad
  3. The New York Stem Cell Foundation Research Institute, New York, New York, USA.

    • Dieter Egli
  4. Mount Sinai Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

    • Miriam Merad
    •  & Brian D Brown
  5. Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

    • Miriam Merad
    •  & Brian D Brown
  6. Diabetes Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

    • Brian D Brown

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Contributions

J.A. designed and performed experiments, analyzed data and wrote the manuscript, A.R., E.S.P., R.S. M.W. and V.K. performed experiments or acquired data, Y.Z. analyzed data, D.E. performed experiments, M.M. designed experiments, analyzed data, and edited the manuscript, B.D.B. designed and supervised the research, analyzed data and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Brian D Brown.

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DOI

https://doi.org/10.1038/nbt.3386

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