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Noninvasive Imaging OX40(+) Activated T Cells Provides Early Warning of Rheumatoid Arthritis
PURPOSE: The goal of this study was to develop an imaging probe—IRDye-680RD-OX40 mAb—that can be used for noninvasive imaging and optical imaging of rheumatoid arthritis (RA). OX40/OX40 ligand (OX40L) interactions have been shown to exert potent costimulatory effects on T cell activation. Detectable...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10333407/ https://www.ncbi.nlm.nih.gov/pubmed/37012517 http://dx.doi.org/10.1007/s11307-023-01819-4 |
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author | Wen, Gang Lei, Hongwei Qi, Baochang Duan, Shao Xiao, Zunyu Han, Chaozhe Xia, Yifei Jing, Chengwei Liu, Jianyu Li, Chao |
author_facet | Wen, Gang Lei, Hongwei Qi, Baochang Duan, Shao Xiao, Zunyu Han, Chaozhe Xia, Yifei Jing, Chengwei Liu, Jianyu Li, Chao |
author_sort | Wen, Gang |
collection | PubMed |
description | PURPOSE: The goal of this study was to develop an imaging probe—IRDye-680RD-OX40 mAb—that can be used for noninvasive imaging and optical imaging of rheumatoid arthritis (RA). OX40/OX40 ligand (OX40L) interactions have been shown to exert potent costimulatory effects on T cell activation. Detectable change in T cell activation profiles was observed in early RA. METHODS: OX40 expression pattern was analyzed by flow cytometry. N-hydroxysuccinimide (NHS) esters are used to label proteins selectively on free amino groups of OX40 monoclonal antibody (mAb). Characterization of IRDye-680RD-OX40 mAb was measured and a fluorescence spectrum gathered. Cell binding assay was also performed between activated and naïve murine T cells. Longitudinal near-infrared fluorescence (NIRF) imaging of the probe was performed on day 8, day 9, day 10, and day 11 of adjuvant-induced arthritis (AIA) mouse model. Paw thickness and body weight were compared between the OX40 mAb and IgG injection groups. RESULTS: NIRF imaging with IRDye-680RD-OX40 mAb revealed strong OX40-positive responses with high specificity. Flow analysis showed that OX40 was specifically expressed on the surface of T cells in RP and spleen of AIA model. The AIA group was significantly differentiated from the control group at all time points with imaging monitoring. The region of interest (ROI) was in line with ex vivo imaging and biodistribution study. This study highlights the potential utility of the OX40 NIRF imaging as a new strategy for RA prediction and T cell monitoring. CONCLUSION: The results provide evidence that IRDye-680RD-OX40 mAb detects organized T cells activation in early RA. The optical probe was capable of detection of RA pathogenesis. It identified transcriptional responses to RA that mediate its immune functions. Thus, it may be an ideal probe for RA imaging. GRAPHICAL ABSTRACT: [Image: see text] |
format | Online Article Text |
id | pubmed-10333407 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-103334072023-07-12 Noninvasive Imaging OX40(+) Activated T Cells Provides Early Warning of Rheumatoid Arthritis Wen, Gang Lei, Hongwei Qi, Baochang Duan, Shao Xiao, Zunyu Han, Chaozhe Xia, Yifei Jing, Chengwei Liu, Jianyu Li, Chao Mol Imaging Biol Research Article PURPOSE: The goal of this study was to develop an imaging probe—IRDye-680RD-OX40 mAb—that can be used for noninvasive imaging and optical imaging of rheumatoid arthritis (RA). OX40/OX40 ligand (OX40L) interactions have been shown to exert potent costimulatory effects on T cell activation. Detectable change in T cell activation profiles was observed in early RA. METHODS: OX40 expression pattern was analyzed by flow cytometry. N-hydroxysuccinimide (NHS) esters are used to label proteins selectively on free amino groups of OX40 monoclonal antibody (mAb). Characterization of IRDye-680RD-OX40 mAb was measured and a fluorescence spectrum gathered. Cell binding assay was also performed between activated and naïve murine T cells. Longitudinal near-infrared fluorescence (NIRF) imaging of the probe was performed on day 8, day 9, day 10, and day 11 of adjuvant-induced arthritis (AIA) mouse model. Paw thickness and body weight were compared between the OX40 mAb and IgG injection groups. RESULTS: NIRF imaging with IRDye-680RD-OX40 mAb revealed strong OX40-positive responses with high specificity. Flow analysis showed that OX40 was specifically expressed on the surface of T cells in RP and spleen of AIA model. The AIA group was significantly differentiated from the control group at all time points with imaging monitoring. The region of interest (ROI) was in line with ex vivo imaging and biodistribution study. This study highlights the potential utility of the OX40 NIRF imaging as a new strategy for RA prediction and T cell monitoring. CONCLUSION: The results provide evidence that IRDye-680RD-OX40 mAb detects organized T cells activation in early RA. The optical probe was capable of detection of RA pathogenesis. It identified transcriptional responses to RA that mediate its immune functions. Thus, it may be an ideal probe for RA imaging. GRAPHICAL ABSTRACT: [Image: see text] Springer International Publishing 2023-04-03 2023 /pmc/articles/PMC10333407/ /pubmed/37012517 http://dx.doi.org/10.1007/s11307-023-01819-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Wen, Gang Lei, Hongwei Qi, Baochang Duan, Shao Xiao, Zunyu Han, Chaozhe Xia, Yifei Jing, Chengwei Liu, Jianyu Li, Chao Noninvasive Imaging OX40(+) Activated T Cells Provides Early Warning of Rheumatoid Arthritis |
title | Noninvasive Imaging OX40(+) Activated T Cells Provides Early Warning of Rheumatoid Arthritis |
title_full | Noninvasive Imaging OX40(+) Activated T Cells Provides Early Warning of Rheumatoid Arthritis |
title_fullStr | Noninvasive Imaging OX40(+) Activated T Cells Provides Early Warning of Rheumatoid Arthritis |
title_full_unstemmed | Noninvasive Imaging OX40(+) Activated T Cells Provides Early Warning of Rheumatoid Arthritis |
title_short | Noninvasive Imaging OX40(+) Activated T Cells Provides Early Warning of Rheumatoid Arthritis |
title_sort | noninvasive imaging ox40(+) activated t cells provides early warning of rheumatoid arthritis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10333407/ https://www.ncbi.nlm.nih.gov/pubmed/37012517 http://dx.doi.org/10.1007/s11307-023-01819-4 |
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