Challenges for labeling and longitudinal tracking of adoptively transferred autoreactive T lymphocytes in an experimental type-1 diabetes model

MAGMA. 2019 Jun;32(3):295-305. doi: 10.1007/s10334-018-0720-x. Epub 2019 Jan 16.

Abstract

Objective: Tracking the autoreactive T-cell migration in the pancreatic region after labeling with fluorinated nanoparticles (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[3-(2-pyridyldithio)propionate]-perfluoro-15-crown-5-ether nanoparticles, PDP-PFCE NPs) in a diabetic murine model using 19F MRI.

Materials and methods: Synthesis of novel PDP-PFCE fluorine tracer was performed for in vitro labeling of T cells. Labeling conditions were optimized using different PDP-PFCE NPs concentrations. For in vivo 19F MRI, mice were longitudinally followed after adoptive transfer of activated, autoreactive, labeled T cells in NOD.SCID mice.

Results: Established MR protocols were used for challenging T cell labeling to track inflammation in a model of diabetes after successful labeling of CD4+ and CD8+ T cells with PDP-PFCE NPs. However, T cells were difficult to be detected in vivo after their engraftment in animals.

Discussion: We showed successful in vitro labeling of T cells using novel fluorinated liposomal nanoparticles. However, insufficient and slow accumulation of labeled T cells and subsequent T cell proliferation in the pancreatic region remains as limitations of in vivo cell imaging by 19F MRI.

Keywords: 19F MRI; Inflammation; Nanoparticles; T cells; Type 1 diabetes.

MeSH terms

  • Adoptive Transfer*
  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / cytology
  • Cell Proliferation
  • Diabetes Mellitus, Experimental / diagnostic imaging*
  • Diabetes Mellitus, Experimental / immunology*
  • Diabetes Mellitus, Type 1 / diagnostic imaging*
  • Diabetes Mellitus, Type 1 / immunology*
  • Disease Models, Animal
  • Fluorine / chemistry
  • Inflammation
  • Isotopes / chemistry
  • Liposomes / chemistry
  • Magnetic Resonance Imaging
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Nanoparticles / chemistry
  • Spleen / metabolism
  • T-Lymphocytes / cytology*
  • Transgenes

Substances

  • Isotopes
  • Liposomes
  • Fluorine