title: Noninvasive Imaging of Human Immune Responses in a Human Xenograft Model of Graft-Versus-Host Disease.
abstract: 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 γ-/- 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.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Catharina H M J
authors.initials: CHMJ
authors.lastname: Van Elssen
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts.|Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Rashidian
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Vrbanac
authors.affiliation: Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts.|Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Kai W
authors.initials: KW
authors.lastname: Wucherpfennig
authors.affiliation: Protein Engineering Group, Leibniz Institute for Molecular Pharmacology and Freie Universität Berlin, Berlin, Germany.
authors.forename: Zeina El
authors.initials: ZE
authors.lastname: Habre
authors.affiliation: Protein Engineering Group, Leibniz Institute for Molecular Pharmacology and Freie Universität Berlin, Berlin, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Sticht
authors.affiliation: Protein Engineering Group, Leibniz Institute for Molecular Pharmacology and Freie Universität Berlin, Berlin, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Freund
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts.|Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts.|Center for Immune Regulation, Oslo University Hospital, University of Oslo, Oslo, Norway.
authors.forename: Johanne T
authors.initials: JT
authors.lastname: Jacobsen
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts.|Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts.
authors.forename: Juanjo
authors.initials: J
authors.lastname: Cragnolini
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts.|Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts.
authors.forename: Jessica
authors.initials: J
authors.lastname: Ingram
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands; and.
authors.forename: Loes
authors.initials: L
authors.lastname: Plaisier
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands; and.
authors.forename: Eric
authors.initials: E
authors.lastname: Spierings
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts.|Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Charlestown, Massachusetts.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Tager
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts ploegh@wi.mit.edu.|Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts.
authors.forename: Hidde L
authors.initials: HL
authors.lastname: Ploegh
mesh_terms: D000818:Animals; D006086:Graft vs Host Disease / Q000000981:diagnostic imaging* / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000276:immunology; D061905:Single-Domain Antibodies / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000949:Histocompatibility Antigens Class II; D019275:Radiopharmaceuticals; D061905:Single-Domain Antibodies
keywords: GvHD; ImmunoPET; humanized mice; single domain antibodies