When it comes to fending off disease and helping prevent people from falling ill, the body's immune system -- armed with T-cells that help eliminate cancer cells, virus-infected cells and more -- is second to none. But exactly how the immune system works remains, in many ways, a mystery, as there are numerous cell types whose functions and interactions with our immune systems have not been well understood. Now, a team of scientists at the Icahn School of Medicine at Mount Sinai have developed the Just EGFP Death-Inducing T-cell, or JEDI T-cells, which enable the visualization of T-cell antigens, allowing researchers to study T-cell interactions with different cell types, model disease states, and finally determine the functions of otherwise poorly characterized cell populations. The article was first published online in Nature Biotechnology.
"JEDI T-cells provide an unprecedented technology to study, model and visualize immune responses and immunotherapies in ways that were never before possible, and this has the potential to revolutionize immunology research," said Brian D. Brown, BSc, PhD, Associate Professor of Genetics and Genomics Sciences at the Icahn School of Medicine at Mount Sinai, and senior author of the paper. "Immunotherapy is considered one of the most important breakthroughs in cancer care in decades, but there is more research needed to improve its success in the clinic. The JEDI technology will be integral to this effort, as well as helping to advance other area of drug development."
Enhanced green fluorescent protein, or EGFP, was first discovered in jellyfish and is what gives these sea creatures their bright luminescence. In 1994, scientists first realized that putting the EGFP gene into cells made them glow green, making it possible to easily visualize them: ever since, scientists have generated thousands of living systems with EGFP, including EGFP-expressing viruses and EGFP-expressing cancer cells.
The JEDI T-cells developed by Dr. Brown and his team at Mount Sinai enable researchers to study T-cells, the assassins of the immune system, as they interact with and kill any cell in the body, including pathogen-infected cells and even tumor cells. This is important because it makes it possible to model almost any autoimmune disease, evaluate new drug therapies, and even identify novel targets in the emerging area of cancer immunotherapies.
Using the JEDI technology, Mount Sinai researchers uncovered evidence that immune cells can find cells in the brain expressing their target antigen, even in non-infected states, which provides evidence of an immune surveillance pathway within the body's central nervous system. This discovery has relevant implications for understanding neuroinflammation and even brain malignancies such as glioblastoma.
"In a galaxy far, far away, the Jedi knights defeated the dark side," said Judith Agudo, PhD, Postdoctoral Fellow at the Icahn School of Medicine at Mount Sinai and first author of the study. "We believe the JEDI T-cells will help us win the fight against cancer, autoimmunity, and infectious disease."
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The article, titled "GFP-specific CD8 T cells enable targeted cell depletion and visualization of T-cell interactions," first appeared online in Nature Biotechnology. Authors are Judith Agudo, Albert Ruzo, Eun Sook Park, Robert Sweeney, Veronika Kana, Meng Wu, Yong Zhao, Dieter Egli, Miriam Merad and Brian D. Brown.
About the Mount Sinai Health System
The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services -- from community-based facilities to tertiary and quaternary care.
The System includes approximately 6,100 primary and specialty care physicians; 12 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. The Mount Sinai Hospital is ranked as one of the nation's top 10 hospitals in Geriatrics, Cardiology/Heart Surgery, and Gastroenterology, and is in the top 25 in five other specialties in the 2014-2015 'Best Hospitals' issue of U.S. News & World Report. Mount Sinai's Kravis Children's Hospital also is ranked in seven out of ten pediatric specialties by U.S. News & World Report. The New York Eye and Ear Infirmary of Mount Sinai is ranked 11th nationally for Ophthalmology, while Mount Sinai Beth Israel is ranked regionally.
For more information, visit http://www.mountsinai.org
Journal
Nature Biotechnology