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In vivo imaging of a diabetogenic CD8+ T cell response during type 1 diabetes progression
Author(s) -
Medarova Zdravka,
Tsai Sue,
Evgenov Natalia,
Santamaria Pere,
Moore Anna
Publication year - 2008
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/mrm.21494
Subject(s) - in vivo , type 2 diabetes , cd8 , type 1 diabetes , diabetes mellitus , medicine , chemistry , nuclear magnetic resonance , endocrinology , biology , immune system , immunology , physics , genetics
Type 1 diabetes is preceded by a long, protracted period of pancreatic islet inflammation by autoreactive lymphocytes. Noninvasive imaging of islet inflammation prior to the onset of hyperglycemia might have diagnostic and therapeutic implications, but this is not currently possible. Here, MRI is used to track, noninvasively, the accumulation diabetogenic CD8+ T‐cells during type 1 diabetes progression in nonobese diabetic (NOD) mice. The contrast agent is an MRI probe (MN‐NRP‐V7) that specifically labels CD8+ T‐cells recognizing residues 206–214 of islet‐specific glucose‐6‐phosphatase catalytic subunit related protein (IGRP 206–214 ) in the context of the major histocompatibility complex (MHC) class I molecule H‐2K d . This probe consists of superparamagnetic iron oxide nanoparticles (MN) coated with K d molecules presenting NRP‐V7, a high‐avidity mimotope of IGRP 206–214 . NOD mice of different ages (5, 8, 15, and 24 weeks) were imaged by MRI before and after a single intravenous injection of MN‐NRP‐V7 or unmodified MN nanoparticles. MN‐NRP‐V7 accumulation, as determined by semiquantitative MRI analysis of pancreas‐associated T 2 relaxation time, was antigen‐specific, age‐dependent, and well correlated with the numbers of MN‐NRP‐V7‐labeled CD8+ T‐cells recovered from the pancreata of the treated mice. Antigen/MHC‐coupled nanoparticles represent a promising new avenue for noninvasive imaging of lymphocyte inflammation in organ‐specific autoimmunity and transplantation. Magn Reson Med, 2008. © 2008 Wiley‐Liss, Inc.