T-cell homing to the pancreas in autoimmune mouse models of diabetes: in vivo MR imaging.

Abstract

To evaluate the efficiency of T-cell labeling with anionic magnetic nanoparticles (AMNPs) and in vivo magnetic resonance (MR) imaging monitoring of T-cell homing to the pancreas. In vivo MR images of pancreas were obtained with a 7-T MR system in 12 NOD (nonobese diabetic) mice at 11 and 20 days after injection of AMNP-loaded or unloaded T cells. Homing of loaded T cells in pancreatic lymph nodes was detected by the presence of a focal dark spot with T2* effect in a caudal area of the pancreas. Detection of loaded T cells in pancreatic islets was evaluated by comparison of histograms of MR signal intensity generated in whole pancreas in mice injected with loaded and unloaded T cells. Homing of loaded T cells was confirmed at transmission electronic microscopy (TEM). Fifty-six mice underwent all experiments. Focal dark spots with T2* effect were observed at 11 days in all three mice injected with loaded T cells and in none of the three mice injected with unloaded T cells. At 20 days, a more diffuse negative enhancement of the whole pancreas was noticed in one mouse injected with loaded T cells than in three mice injected with unloaded T cells. Presence of loaded T cells was confirmed with TEM. In vitro and in vivo tests confirmed that survival and function were not altered by loading. The ability of MR imaging to depict cell homing in living organisms at least 20 days after cell labeling was demonstrated, opening the way of follow-up in autoimmune diseases and cell therapy.