PMID- 12928772
OWN - NLM
STAT- MEDLINE
DCOM- 20040130
LR  - 20181113
IS  - 0012-186X (Print)
IS  - 0012-186X (Linking)
VI  - 46
IP  - 10
DP  - 2003 Oct
TI  - Autoantigen-specific protection of non-obese diabetic mice from 
      cyclophosphamide-accelerated diabetes by vaccination with dendritic cells.
PG  - 1357-65
AB  - AIMS/HYPOTHESIS: Dendritic cells (DCs) are professional antigen presenting cells 
      involved in the initiation of primary immune responses and the preservation of 
      peripheral tolerance. The aim of this study was to develop a DC vaccine for 
      autoantigen-specific prevention of autoimmune diabetes. METHODS: Splenocytes from 
      diabetes-prone NOD mice were cultured in conditioned media to obtain a 
      homogeneous DC sub-population for vaccination experiments. These cells were used 
      to modulate autoimmune responses in NOD mice after synchronization of diabetes 
      with cyclophosphamide. After immunisation with insulin-pulsed DCs the incidence 
      of diabetes, the insulitis grade and the cytokine production was examined. 
      RESULTS: The long-term culture of splenocytes resulted in the generation of a 
      cell line, termed NOD-DC1, which have a phenotype of myeloid DCs (CD11c, CD11b, 
      DEC-205), express MHC class II and co-stimulatory molecules (CD40, CD80, CD86). 
      The NOD-DC1 cells have preserved functional activity shown by the detection of a 
      high antigen uptake capacity, the induction of a mixed lymphocyte reaction and 
      stimuli-dependent IL-6 and TNF-alpha secretion. Vaccination with insulin-pulsed 
      NOD-DC1 cells results in an antigen-specific prevention of diabetes. This was 
      mediated by a reduction of the severity of insulitis and a decrease of T helper 1 
      effector cells. CONCLUSION/INTERPRETATION: We describe the generation of a DC 
      line which confers protection from diabetes in an antigen-specific way. Our data 
      shows that autoantigen-loaded DCs can induce strong immunoregulatory effects 
      supporting the hypothesis that DCs are promising candidates to develop novel 
      vaccines for the prevention of autoimmune diabetes.
FAU - Krueger, T
AU  - Krueger T
AD  - German Diabetes Research Institute, University of Dusseldorf, 40225, Dusseldorf, 
      Germany.
FAU - Wohlrab, U
AU  - Wohlrab U
FAU - Klucken, M
AU  - Klucken M
FAU - Schott, M
AU  - Schott M
FAU - Seissler, J
AU  - Seissler J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20030820
PL  - Germany
TA  - Diabetologia
JT  - Diabetologia
JID - 0006777
RN  - 0 (Autoantigens)
RN  - 0 (Epitopes)
RN  - 0 (Immunosuppressive Agents)
RN  - 130068-27-8 (Interleukin-10)
RN  - 8N3DW7272P (Cyclophosphamide)
SB  - IM
MH  - Animals
MH  - Autoantigens/*immunology
MH  - Cell Line
MH  - Cyclophosphamide/pharmacology
MH  - Dendritic Cells/drug effects/*immunology/*transplantation
MH  - Diabetes Mellitus, Type 1/*physiopathology/*prevention & control
MH  - Epitopes
MH  - Female
MH  - Immunosuppressive Agents/pharmacology
MH  - Interleukin-10/pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred NOD
MH  - NIH 3T3 Cells
MH  - *Vaccination/methods
EDAT- 2003/08/21 05:00
MHDA- 2004/01/31 05:00
CRDT- 2003/08/21 05:00
PHST- 2003/02/14 00:00 [received]
PHST- 2003/06/30 00:00 [revised]
PHST- 2003/08/21 05:00 [pubmed]
PHST- 2004/01/31 05:00 [medline]
PHST- 2003/08/21 05:00 [entrez]
AID - 10.1007/s00125-003-1199-0 [doi]
PST - ppublish
SO  - Diabetologia. 2003 Oct;46(10):1357-65. doi: 10.1007/s00125-003-1199-0. Epub 2003 
      Aug 20.