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Bioluminescent Reporting of In Vivo IFN-γ Immune Responses during Infection and Autoimmunity

Reynolds, CJ; Chong, DLW; Li, Y; Black, SL; Cutler, A; Webster, Z; Manji, J; ... Boyton, RJ; + view all (2019) Bioluminescent Reporting of In Vivo IFN-γ Immune Responses during Infection and Autoimmunity. Journal of Immunology , 202 (6) , Article 1647. 10.4049/jimmunol.1801453. Green open access

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Abstract

IFN-γ is a key cytokine of innate and adaptive immunity. It is important to understand temporal changes in IFN-γ production and how these changes relate to the role of IFN-γ in diverse models of infectious and autoimmune disease, making the ability to monitor and track IFN-γ production in vivo of a substantial benefit. IFN-γ ELISPOTs have been a central methodology to measure T cell immunity for many years. In this study, we add the capacity to analyze IFN-γ responses with high sensitivity and specificity, longitudinally, in vitro and in vivo. This allows the refinement of experimental protocols because immunity can be tracked in real-time through a longitudinal approach. We have generated a novel murine IFN-γ reporter transgenic model that allows IFN-γ production to be visualized and quantified in vitro and in vivo as bioluminescence using an imaging system. At baseline, in the absence of an inflammatory stimulus, IFN-γ signal from lymphoid tissue is detectable in vivo. Reporter transgenics are used in this study to track the IFN-γ response to Pseudomonas aeruginosa infection in the lung over time in vivo. The longitudinal development of the adaptive T cell immunity following immunization with Ag is identified from day 7 in vivo. Finally, we show that we are able to use this reporter transgenic to follow the onset of autoimmune T cell activation after regulatory T cell depletion in an established model of systemic autoimmunity. This IFN-γ reporter transgenic, termed "Gammaglow," offers a valuable new modality for tracking IFN-γ immunity, noninvasively and longitudinally over time.

Type: Article
Title: Bioluminescent Reporting of In Vivo IFN-γ Immune Responses during Infection and Autoimmunity
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.4049/jimmunol.1801453
Publisher version: https://doi.org/10.4049/jimmunol.1801453
Language: English
Additional information: This work is licensed under a CC BY 4.0 Unported license. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit: https://creativecommons.org/licenses/by/4.0/
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Nephrology
URI: https://discovery.ucl.ac.uk/id/eprint/10070008
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