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the entire tumor simultaneously, it was observed that CD8 + T cells were
recruited primarily to focal regions within the tumor and areas of the tumor
capsules ( Figure 4.1 D). Interestingly, when subsequent infusions of labeled
CD8 + T cells were administered, their point of infiltration into the tumors
demonstrated little overlap with the previously infused CD8 + T cells. When
recruitment of CTL was followed over a longer time period, heterogeneity
of CD8 + T-cell recruitment was again observed. This alteration in the CD8 +
T-cell recruitment patterns correlated to temporal patterns of recirculation
through the draining lymph nodes. Taken together, the results of this study
indicated a spatially and temporally heterogeneous recruitment pattern of
anti-tumor CD8 + T cells to tumor sites and that multiple administrations of
CD8 + T cells could be a more effective therapy for tumors.
Another study focused on imaging of DCs following allogeneic bone mar-
row transplantation [114] . The purpose of this study was to evaluate whether
rapamycin (RAPA) treatment of DCs, which can result in tolerogenic function,
would affect their migratory ability. Dendritic cells were labeled by phagocy-
tosis of SPIO nanoparticles directly coupled to a murine IgG Ab labeled with
FITC. The labeling of the DCs did not appear to have a significant impact
on their phenotype or function. The expression of CD80, CD86, CD40 and
MHC class II was similar on labeled DCs as compared to control DCs, as was
their migration and their ability to induce T-cell proliferation in vitro . After
local intramuscular injection of SPIO-labeled DCs into the leg, the DCs
migrated from this site towards inguinal, mesenteric, axillary and cervical
lymph node compartments. When the SPIO-labeled DCs were conditioned
with RAPA in vitro before injection, followed by injection of RAPA in vivo , no
alteration in their migration was observed.
74
Multimodal imaging of GVHD and anti-tumor
responses
The use of multiple modalities in imaging studies can be a very powerful
technique as the strength of each modality can be combined to overcome
each modality's relative weakness. For example, while PET has exquisite
tissue penetrating ability and sensitivity, it is usually combined with CT of
X-ray images to provide the requisite spatial information for the imaged
tracers. This also applies to bioluminescence in animal models which can
be combined with CT or MRI to give more accurate localization of the BLI
cells within a living animal.
Agger et al. presented a method of tracking T cells via a combination of PET
and MRI which combined the high sensitivity of PET with the high resolu-
tion of MRI [115] . CD8 + T cells, which were isolated from transgenic OT-1
mice and react to the ovalbumin peptide SIINFEKL, were labeled with 124 I
and adoptively transferred into host mice which had an ovalbumin-positive
melanoma. After 5 days, 124 I-labele d CD8 + T cells could be clearly visualized
by PET at the tumor site. Accurate overlay of PET data sets to MRI data sets
was achievable, which provided a high level of anatomical information and
accurate localization of the tumor-infiltrating lymphocytes.
A novel imaging strategy was developed by Na et al. to monitor immune cell
trafficking and activation of NFAT following allogeneic transplantation [116] .
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