PMID- 12727648
OWN - NLM
STAT- MEDLINE
DCOM- 20030619
LR  - 20190616
IS  - 0077-8923 (Print)
IS  - 0077-8923 (Linking)
VI  - 987
DP  - 2003 Apr
TI  - Tolerogenic dendritic cells induced by vitamin D receptor ligands enhance 
      regulatory T cells inhibiting autoimmune diabetes.
PG  - 258-61
AB  - Dendritic cells (DCs) not only induce but also modulate T cell activation. 
      1,25-Dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] induces DCs with a tolerogenic 
      phenotype, characterized by decreased expression of CD40, CD80, and CD86 
      co-stimulatory molecules, low IL-12, and enhanced IL-10 secretion. We have found 
      that a short treatment with 1,25-(OH)(2)D(3) induces tolerance to fully 
      mismatched mouse islet allografts, and that this tolerance is stable to challenge 
      with donor-type spleen cells and allows acceptance of donor-type vascularized 
      heart grafts. This effect is enhanced by co-administration of mycophenolate 
      mofetil (MMF), a selective inhibitor of T and B cell proliferation, that also has 
      effects similar to 1,25-(OH)(2)D(3) on DCs. Graft acceptance is associated with 
      impaired development of type 1 CD4(+) and CD8(+) cells and an increased 
      percentage of CD4(+)CD25(+) regulatory cells expressing CD152 in the spleen and 
      in the draining lymph node. Transfer of CD4(+)CD25(+) cells from tolerant mice 
      protects 100% of the syngeneic recipients from islet allograft rejection. 
      CD4(+)CD25(+) cells that are able to inhibit the T cell response to a pancreatic 
      autoantigen and to significantly delay disease transfer by pathogenic 
      CD4(+)CD25(-) cells are also induced by treatment of adult nonobese diabetic 
      (NOD) mice with a selected vitamin D receptor (VDR) ligand. This treatment 
      arrests progression of insulitis and Th1 cell infiltration, and inhibits diabetes 
      development at non-hypercalcemic doses. The enhancement of CD4(+)CD25(+) 
      regulatory T cells able to mediate transplantation tolerance and to arrest type 1 
      diabetes development by a short oral treatment with small organic compounds that 
      induce tolerogenic DCs, like VDR ligands, suggests possible clinical applications 
      of this approach.
FAU - Adorini, Luciano
AU  - Adorini L
AD  - BioXell, Via Olgettina 58, I-20132 Milano, Italy. Luciano.Adorini@bioxell.com
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Ann N Y Acad Sci
JT  - Annals of the New York Academy of Sciences
JID - 7506858
RN  - 0 (Ligands)
RN  - 0 (Receptors, Calcitriol)
SB  - IM
MH  - Animals
MH  - Autoimmune Diseases/*immunology
MH  - Dendritic Cells/*immunology
MH  - Diabetes Mellitus, Type 1/*immunology
MH  - Ligands
MH  - Mice
MH  - Receptors, Calcitriol/immunology/*metabolism
MH  - T-Lymphocytes/*immunology
RF  - 10
EDAT- 2003/05/03 05:00
MHDA- 2003/06/20 05:00
CRDT- 2003/05/03 05:00
PHST- 2003/05/03 05:00 [pubmed]
PHST- 2003/06/20 05:00 [medline]
PHST- 2003/05/03 05:00 [entrez]
AID - 10.1111/j.1749-6632.2003.tb06057.x [doi]
PST - ppublish
SO  - Ann N Y Acad Sci. 2003 Apr;987:258-61. doi: 10.1111/j.1749-6632.2003.tb06057.x.