Imaging TCR-Dependent NFAT-Mediated T-Cell Activation with Positron Emission Tomography In Vivo
A noninvasive method for molecular imaging of T-cell activity in vivo would be of considerable value. It would aid in understanding the role of specific genes and signal transduction pathways in the course of normal and pathologic immune responses, could elucidate temporal dynamics and immune regula...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2001-01-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558601800038 |
| _version_ | 1819030753424441344 |
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| author | Vladimir Ponomarev Michael Doubrovin Clay Lyddane Tatiana Beresten Julius Balatoni William Bornman Ronald Finn Timothy Akhurst Steven Larson Ronald Blasberg Michel Sadelain Juri Gelovani Tjuvajev |
| author_facet | Vladimir Ponomarev Michael Doubrovin Clay Lyddane Tatiana Beresten Julius Balatoni William Bornman Ronald Finn Timothy Akhurst Steven Larson Ronald Blasberg Michel Sadelain Juri Gelovani Tjuvajev |
| author_sort | Vladimir Ponomarev |
| collection | DOAJ |
| description | A noninvasive method for molecular imaging of T-cell activity in vivo would be of considerable value. It would aid in understanding the role of specific genes and signal transduction pathways in the course of normal and pathologic immune responses, could elucidate temporal dynamics and immune regulation at different stages of disease and following therapy. We developed and assessed a novel method for monitoring the T-cell receptor (TCR) -dependent nuclear factor of activated T cells (NFAT) -mediated activation of T cells by optical fluorescence imaging (OFI) and positron emission tomography (PET). The herpes simplex virus type 1 thymidine kinase/green fluorescent protein [HSV1-tk/GFP (TKGFP) ] dual reporter gene was used to monitor NFAT-mediated transcriptional activation in human Jurkat cells. A recombinant retrovirus bearing the NFAT-TKGFP reporter system was constructed in which the TKGFP reporter gene was placed under control of an artificial cis-acting NFAT-specific enhancer. Transduced Jurkat cells were used to establish subcutaneous infiltrates in nude rats. We demonstrated that noninvasive OR and nuclear imaging of T-cell activation is feasible using the NFAT-TKGFP reporter system. PET imaging with [124]FIAU using the NFAT-TKGFP reporter system is sufficiently sensitive to detect T-cell activation in vivo. PET images were confirmed by independent measurements of T-cell activation (e.g., CD69) and induction of GFP fluorescence. PET imaging of TCR-induced NFAT-dependent transcriptional activity may be useful in the assessment of T cell responses, T-cell-based adoptive therapies, vaccination strategies and immunosuppressive drugs. |
| first_indexed | 2024-12-21T06:35:10Z |
| format | Article |
| id | doaj.art-7041a0c094e34993ba84cd45c0f9875e |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-21T06:35:10Z |
| publishDate | 2001-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-7041a0c094e34993ba84cd45c0f9875e2022-12-21T19:12:53ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022001-01-013648048810.1038/sj.neo.7900204Imaging TCR-Dependent NFAT-Mediated T-Cell Activation with Positron Emission Tomography In VivoVladimir Ponomarev0Michael Doubrovin1Clay Lyddane2Tatiana Beresten3Julius Balatoni4William Bornman5Ronald Finn6Timothy Akhurst7Steven Larson8Ronald Blasberg9Michel Sadelain10Juri Gelovani Tjuvajev11Departments of Neurology and Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10021Departments of Neurology and Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10021Immunology Program, Gene Transfer and Somatic Cell Engineering Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10021Departments of Neurology and Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10021Radiochemistry/Cyclotron Core FaciIity, Memorial Sloan Kettering Cancer Center, New York, NY 10021Preparative Synthesis Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10021Radiochemistry/Cyclotron Core FaciIity, Memorial Sloan Kettering Cancer Center, New York, NY 10021Nuclear Medicine Service, Memorial Sloan Kettering Cancer Center, New York, NY 10021Preparative Synthesis Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10021Departments of Neurology and Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10021Immunology Program, Gene Transfer and Somatic Cell Engineering Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10021Departments of Neurology and Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10021A noninvasive method for molecular imaging of T-cell activity in vivo would be of considerable value. It would aid in understanding the role of specific genes and signal transduction pathways in the course of normal and pathologic immune responses, could elucidate temporal dynamics and immune regulation at different stages of disease and following therapy. We developed and assessed a novel method for monitoring the T-cell receptor (TCR) -dependent nuclear factor of activated T cells (NFAT) -mediated activation of T cells by optical fluorescence imaging (OFI) and positron emission tomography (PET). The herpes simplex virus type 1 thymidine kinase/green fluorescent protein [HSV1-tk/GFP (TKGFP) ] dual reporter gene was used to monitor NFAT-mediated transcriptional activation in human Jurkat cells. A recombinant retrovirus bearing the NFAT-TKGFP reporter system was constructed in which the TKGFP reporter gene was placed under control of an artificial cis-acting NFAT-specific enhancer. Transduced Jurkat cells were used to establish subcutaneous infiltrates in nude rats. We demonstrated that noninvasive OR and nuclear imaging of T-cell activation is feasible using the NFAT-TKGFP reporter system. PET imaging with [124]FIAU using the NFAT-TKGFP reporter system is sufficiently sensitive to detect T-cell activation in vivo. PET images were confirmed by independent measurements of T-cell activation (e.g., CD69) and induction of GFP fluorescence. PET imaging of TCR-induced NFAT-dependent transcriptional activity may be useful in the assessment of T cell responses, T-cell-based adoptive therapies, vaccination strategies and immunosuppressive drugs.http://www.sciencedirect.com/science/article/pii/S1476558601800038molecular imagingT- cell activationherpes virus type 1 thymidine kinaseFIAUPET |
| spellingShingle | Vladimir Ponomarev Michael Doubrovin Clay Lyddane Tatiana Beresten Julius Balatoni William Bornman Ronald Finn Timothy Akhurst Steven Larson Ronald Blasberg Michel Sadelain Juri Gelovani Tjuvajev Imaging TCR-Dependent NFAT-Mediated T-Cell Activation with Positron Emission Tomography In Vivo Neoplasia: An International Journal for Oncology Research molecular imaging T- cell activation herpes virus type 1 thymidine kinase FIAU PET |
| title | Imaging TCR-Dependent NFAT-Mediated T-Cell Activation with Positron Emission Tomography In Vivo |
| title_full | Imaging TCR-Dependent NFAT-Mediated T-Cell Activation with Positron Emission Tomography In Vivo |
| title_fullStr | Imaging TCR-Dependent NFAT-Mediated T-Cell Activation with Positron Emission Tomography In Vivo |
| title_full_unstemmed | Imaging TCR-Dependent NFAT-Mediated T-Cell Activation with Positron Emission Tomography In Vivo |
| title_short | Imaging TCR-Dependent NFAT-Mediated T-Cell Activation with Positron Emission Tomography In Vivo |
| title_sort | imaging tcr dependent nfat mediated t cell activation with positron emission tomography in vivo |
| topic | molecular imaging T- cell activation herpes virus type 1 thymidine kinase FIAU PET |
| url | http://www.sciencedirect.com/science/article/pii/S1476558601800038 |
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