Assessment of migration of HIV-1-loaded dendritic cells labeled with 111In-oxine used as a therapeutic vaccine in HIV-1-infected patients.
Monocyte-derived dendritic cells (DCs) loaded with heat-inactivated HIV are used in therapeutic immunizations. It is not known whether they migrate in vivo to lymph nodes. We used an (111)In-oxine-labeled DC (ILDC) method to visualize the migration of DCs. The activity, time and incubation medium were investigated to obtain the highest cellular viability and radiolabeling yield. A trypan-blue exclusion test was used to determine the cellular viability. In five patients, 2 x 10(6) ILDCs were injected subcutaneously in the arm. An initial dynamic study was performed during the first 5 min after injection. This was followed by static acquisitions at several time points, using a high-resolution (general electric) gamma-camera and quantifying the activity at regions of interest drawn on the injection point. The sensitivity of the gamma-camera was evaluated. The highest number of viable DCs (>83%) and the best radiolabeling yield (>70%) were obtained with 1.11 MBq (111)In-oxine, after 10 min of incubation at 37 degrees C in sodium chloride solution 0.9%. We did not observe migration of ILDCs to local lymph nodes in any patient. However, focal uptake at the place of injection continued during the study period. We observed a higher than expected loss of activity from the injection point (median A(t)/A(0) = 0.60 at day 2), which correlated with an increase in total cytotoxic T lymphocytes (CD8(+) and granzyme B(+) cells) in the lypmphoid tissue observed after immunization (R(2) = 0.92, p = 0.03). If more than 20,000 ILDCs had migrated, they could have been detected. In future trials, a higher number of DCs or alternative methods should be used to assess the migration of DCs to lymph nodes.
Ruiz
Alba
A
Infectious Diseases Unit, Hospital Clínic, Villarroel 170, Barcelona, Spain.
Nomdedeu
Meritxell
M
Ortega
Marisa
M
Lejeune
Merylene
M
Setoain
Javier
J
Climent
Núria
N
Fumero
Emilio
E
Plana
Montserrat
M
León
Agathe
A
Alós
Llucia
L
Piera
Carlos
C
Lomeña
Francisco
F
Gatell
Jose M
JM
Gallart
Teresa
T
García
Felipe
F
D002452:Cell Count; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D015658:HIV Infections / Q000276:immunology / Q000628:therapy*; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology / Q000821:virology; D008213:Lymphocyte Activation; D009000:Monocytes / Q000473:pathology; D009942:Organometallic Compounds / Q000378:metabolism; D015125:Oxyquinoline / Q000031:analogs & derivatives / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014612:Vaccines
D009942:Organometallic Compounds; D014612:Vaccines; C032950:indium oxine; D015125:Oxyquinoline