Magnetic resonance imaging of activated proliferating rhesus macaque T cells labeled with superparamagnetic monocrystalline iron oxide nanoparticles.

Abstract

Imaging of adoptively transferred cells in vivo by magnetic resonance imaging (MRI) could provide important information on disease-related patterns of lymphocyte homing in nonhuman primate models of AIDS. As a preliminary study to assess the feasibility of visualizing activated rhesus T cells by MRI, anti-CD3/CD28-expanded CD4+ T lymphocytes were labeled in vitro with monocrystalline iron oxide nanoparticles (MION). Intracellular incorporation of MION was determined by transmission electron microscopy (TEM) and inductively coupled plasma mass spectrography (ICP-MS). Pretreatment with colchicine did not affect MION labeling, suggesting that cellular uptake of MION occurred by adsorptive pinocytosis or receptor-mediated endocytosis. TEM analysis revealed that MION were intracellularly compartmentalized exclusively in the cytoplasm and did not cause any measurable physiologic effects on T-cell function, including viability, proliferation, synthesis of select cytokines (interleukin [IL]-2, IL-4, IL-6, IL-10, tumor necrosis factor-alpha, and interferon-gamma), activation antigens (CD25 and CD69), adhesion molecules (alpha4beta7 and CD49d), and susceptibility to in vitro infection with simian immunodeficiency virus mac239. A sensitivity of 0.05% (1 MION-labeled T cell in 2000 unlabeled cells) could be achieved using T2-weighted gradient echo imaging. Furthermore, under these experimental conditions, the MRI signal did not decrease in proliferating MION-labeled CD4+ T cells over a period of 120 hours. These results indicate that intracellular labeling with MION can be a useful technique for noninvasively monitoring trafficking patterns of adoptively transferred leukocyte subsets in real-time by MRI in nonhuman primate models of AIDS.

• Authors: J Bruce Sundstrom, Hui Mao, Robert Santoianni, Francois Villinger, Dawn M Little, Toai T Huynh, Ann E Mayne, Encai Hao, Aftab A Ansari
• Journal: Journal of acquired immune deficiency syndromes (1999) (J Acquir Immune Defic Syndr) Vol. 35 Issue 1 Pg. 9-21 (Jan 01 2004) ISSN: 1525-4135 [Print] United States
• PMID: 14707787 (Publication Type: Evaluation Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cell Adhesion Molecules
• Cytokines
• Oxides
• Iron
• Ferrosoferric Oxide

Topics

• Adoptive Transfer
• Animals
• CD4-Positive T-Lymphocytes (metabolism)
• Cell Adhesion Molecules (metabolism)
• Cytokines (metabolism)
• Ferrosoferric Oxide
• Iron (metabolism, pharmacology)
• Lymphocyte Activation
• Macaca mulatta
• Magnetic Resonance Imaging
• Microscopy, Electron
• Oxides (metabolism, pharmacology)
• Simian Immunodeficiency Virus (drug effects)