Magnetic resonance imaging of activated proliferating rhesus macaque T cells labeled with superparamagnetic monocrystalline iron oxide nanoparticles.
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.
Sundstrom
J Bruce
JB
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Woodruff Memorial Building, Room 2335A, 1639 Pierce Drive, Atlanta, GA, USA. jsundst@emory.edu
Mao
Hui
H
Santoianni
Robert
R
Villinger
Francois
F
Little
Dawn M
DM
Huynh
Toai T
TT
Mayne
Ann E
AE
Hao
Encai
E
Ansari
Aftab A
AA
D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D052203:Ferrosoferric Oxide; D007501:Iron / Q000378:metabolism* / Q000494:pharmacology; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D008854:Microscopy, Electron; D010087:Oxides / Q000378:metabolism* / Q000494:pharmacology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects
D015815:Cell Adhesion Molecules; D016207:Cytokines; D010087:Oxides; D007501:Iron; D052203:Ferrosoferric Oxide