A rapid method for labelling CD4+ T cells with ultrasmall paramagnetic iron oxide nanoparticles for magnetic resonance imaging that preserves proliferative, regulatory and migratory behaviour in vitro

A number of techniques have been developed to track the migration of T cells in vivo, but they all suffer significant shortcomings, including the examination of selected organs rather than the organism as a whole — thus precluding longitudinal studies — or limitations imposed by poor spatial resolution and the application of ionizing radiation. By conjugating the HIV tat peptide to ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles in a reaction yielding a mean valence of 45, a magnetic resonance (MR) contrast agent was synthesised that allowed T cells to be efficiently labelled within just 5 min. The USPIO nanoparticles were incorporated into both the cytoplasm and nucleus of labelled cells, which retained normal in vitro proliferative responses to a polyclonal stimulus; suppressive responses mediated by labelled CD4+ CD25+ regulatory T cells; chemotactic responses to the chemokine CXCL-12; and transmigration of an activated endothelial monolayer. We believe that this rapid, efficient and essentially non-toxic approach to labelling both murine and human T cells for MRI holds considerable promise, paving the way for the wider immunological application of this exciting technology.