In vivo magnetic resonance imaging of dendritic cell migration into the draining lymph nodes of mice.
Dendritic cell (DC) migration into the draining lymph nodes is critical for T cell priming. Here, we show that magnetic resonance imaging (MRI) can be used to visualize DC migration in vivo. We combined clinically approved small particles of iron oxide (SPIO) with protamine sulfate to achieve efficient uptake by murine bone marrow-derived DC. SPIO-DC were largely unaltered and after injection into the footpads of mice, they migrated into the T cell areas of the draining lymph nodes, which could be visualized by MRI. Distinct MRI signal reduction patterns correlated with the detection of SPIO-DC mainly within Thy-1.2+ B220- T cell areas, as confirmed by iron staining and immunohistology. Clear signal reduction patterns could still be observed with 1x10(6) injected SPIO-DC at high resolution, resulting in the detection of about 2000 DC. Control injections of homing-incompetent SPIO-DC derived from CCR7-/- mice or SPIO alone did not reach the T cell areas. Taken together, the results demonstrate that clinically approved contrast agents allow the non-invasive visualization of DC migration into the draining lymph node by MRI in vivo at high resolution. This protocol therefore also allows dynamic imaging of immune responses and MRI-based tracking of human DC in patients.
Baumjohann
Dirk
D
Department of Dermatology, University of Erlangen, Erlangen, Germany.
Hess
Andreas
A
Budinsky
Lubos
L
Brune
Kay
K
Schuler
Gerold
G
Lutz
Manfred B
MB
D000818:Animals; D002634:Chemotaxis, Leukocyte; D003287:Contrast Media; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D005290:Ferric Compounds; D005434:Flow Cytometry; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000648:ultrastructure*; D008213:Lymphocyte Activation / Q000276:immunology; D008279:Magnetic Resonance Imaging; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011479:Protamines; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000276:immunology
C515370:CCR7 protein, human; C515371:Ccr7 protein, mouse; D003287:Contrast Media; D005290:Ferric Compounds; D011479:Protamines; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; C000499:ferric oxide