Noninvasive Imaging of Human Immune Responses in a Human Xenograft Model of Graft-Versus-Host Disease

Catharina H. M. J. Van Elssen, Mohammad Rashidian, Vladimir Vrbanac, Kai W. Wucherpfennig, Zeina el Habre, Jana Sticht, Christian Freund, Johanne T. Jacobsen, Juanjo Cragnolini, Jessica Ingram, Loes Plaisier, Eric Spierings, Andrew M. Tager, Hidde L. Ploegh*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

30 Citations (Web of Science)

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 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.

Original languageEnglish
Pages (from-to)1003-1008
Number of pages6
JournalJournal of Nuclear Medicine
Volume58
Issue number6
DOIs
Publication statusPublished - 1 Jun 2017

Keywords

  • GvHD
  • single domain antibodies
  • ImmunoPET
  • humanized mice
  • POSITRON EMISSION TOMOGRAPHY
  • CLASS-II EXPRESSION
  • IN-VIVO
  • ANTIBODY FRAGMENTS
  • MAGIC BULLET
  • PEPTIDE
  • PET
  • CANCER
  • MICE
  • GENERATION

Cite this