Noninvasive Imaging of Human Immune Responses in a Human Xenograft Model of Graft-Versus-Host Disease
| Autor: | Zeina El Habre, Vladimir Vrbanac, Eric Spierings, Loes Plaisier, Juanjo Cragnolini, Catharina H. M. J. Van Elssen, Hidde L. Ploegh, Kai W. Wucherpfennig, Andrew M. Tager, Mohammad Rashidian, Jana Sticht, Johanne T. Jacobsen, Christian Freund, Jessica R. Ingram |
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| Přispěvatelé: | MUMC+: MA Med Staf Artsass Interne Geneeskunde (9), RS: FHML non-thematic output |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
T-Lymphocytes POSITRON EMISSION TOMOGRAPHY Immunology Graft vs Host Disease medicine.disease_cause Major histocompatibility complex ImmunoPET Autoimmunity 03 medical and health sciences 0302 clinical medicine Immune system Antigen single domain antibodies Immunity medicine Animals Humans Radiology Nuclear Medicine and imaging PEPTIDE IN-VIVO Mice Knockout GvHD MAGIC BULLET biology business.industry Histocompatibility Antigens Class II CLASS-II EXPRESSION Single-Domain Antibodies medicine.disease CANCER Immunity Innate MICE 030104 developmental biology Graft-versus-host disease humanized mice PET ANTIBODY FRAGMENTS 030220 oncology & carcinogenesis Positron-Emission Tomography Humanized mouse biology.protein Antibody Radiopharmaceuticals business GENERATION |
| Zdroj: | Journal of Nuclear Medicine, 58(6), 1003-1008. Society of Nuclear Medicine and Molecular Imaging |
| ISSN: | 1535-5667 0161-5505 |
| Popis: | The immune system plays a crucial role in many diseases. Activation or suppression of immunity is often related to clinical outcome. Methods to explore the dynamics of immune responses are important to elucidate their role in conditions characterized by inflammation, such as infectious disease, cancer, or autoimmunity. Immuno-PET is a noninvasive method by which disease and immune cell infiltration can be explored simultaneously. Using radiolabeled antibodies or fragments derived from them, it is possible to image disease-specific antigens and immune cell subsets. Methods: We developed a method to noninvasively image human immune responses in a relevant humanized mouse model. We generated a camelid-derived single-domain antibody specific for human class II major histocompatibility complex products and used it to noninvasively image human immune cell reconstitution in nonobese diabetic severe combined immune deficiency gamma-/- mice reconstituted with human fetal thymus, liver, and liver-derived hematopoietic stem cells (BLT mice). Results: We showed imaging of infiltrating immunocytes in BLT mice that spontaneously developed a graft-versus-host-like condition, characterized by alopecia and blepharitis. In diseased animals, we showed an increased PET signal in the liver, attributable to infiltration of activated class II major histocompatibility complex(+) T cells. Conclusion: Noninvasive imaging of immune infiltration and activation could thus be of importance for diagnosis and evaluation of treatment of graft-versus-host disease and holds promise for other diseases characterized by inflammation. |
| Databáze: | OpenAIRE |
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