Bioluminescent reporting of in vivo interferon gamma immune responses during infection and autoimmunity

Title: Bioluminescent reporting of in vivo interferon gamma immune responses during infection and autoimmunity
Authors: Boyton, R
Reynolds, C
Chong, D
Li, Y
Black, L
Cutler, A
Webster, Z
Manji, J
Altmann, D
Item Type: Journal Article
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.
Issue Date: 8-Apr-2019
Date of Acceptance: 30-Jan-2019
URI: http://hdl.handle.net/10044/1/73007
DOI: https://doi.org/10.4049/jimmunol.1801453
ISSN: 1550-6606
Publisher: American Association of Immunologists
Start Page: 2502
End Page: 2510
Journal / Book Title: Journal of Immunology
Volume: 202
Issue: 8
Copyright Statement: © 2019 The Authors. This article is distributed under the terms of the CC BY 4.0 Unported license (http://creativecommons.org/licenses/by/4.0/).
Sponsor/Funder: Welton Foundation
National Institutes of Health
Biotechnology and Biological Sciences Research Council (BBSRC)
Imperial College Healthcare NHS Trust- BRC Funding
Funder's Grant Number: N/A
HHSN272200900046C
BB/H005439/1
RDF01 79560
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
REGULATORY T-CELLS
INTERFERON-GAMMA
TH17 CELLS
MICE
EXPRESSION
DEFECTS
NK
1107 Immunology
Immunology
Publication Status: Published
Online Publication Date: 2019-04-08
Appears in Collections:Clinical Sciences
Molecular Sciences



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