PMID- 12562382
OWN - NLM
STAT- MEDLINE
DCOM- 20030407
LR  - 20190513
IS  - 0009-9104 (Print)
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Linking)
VI  - 131
IP  - 2
DP  - 2003 Feb
TI  - Dendritic cells infected with adenovirus expressing the thyrotrophin receptor 
      induce Graves' hyperthyroidism in BALB/c mice.
PG  - 234-40
AB  - Dendritic cells (DCs) are the most potent antigen-presenting cells and a 
      prerequisite for the initiation of primary immune response. This study was 
      performed to investigate the contribution of DCs to the initiation of Graves' 
      hyperthyroidism, an organ-specific autoimmune disease in which the thyrotrophin 
      receptor (TSHR) is the major autoantigen. DCs were prepared from bone marrow 
      precursor cells of BALB/c mice by culturing with granulocyte macrophage-colony 
      stimulating factor and interleukin-4. Subcutaneous injections of DCs infected 
      with recombinant adenovirus expressing the TSHR (but not beta-galactosidase) in 
      syngeneic female mice induced Graves'-like hyperthyroidism (8 and 35% of mice 
      after two and three injections, respectively) characterized by stimulating TSHR 
      antibodies, elevated serum thyroxine levels and diffuse hyperplasitc goiter. TSHR 
      antibodies determined by ELISA were of both IgG1 (Th2-type) and IgG2a (Th1-type) 
      subclasses, and splenocytes from immunized mice secreted interferon-gamma (a Th1 
      cytokine), not interleukin-4 (a Th2 cytokine), in response to TSHR antigen. 
      Surprisingly, IFN-gamma secretion, and induction of antibodies and disease were 
      almost completely suppressed by co-administration of alum/pertussis toxin, a 
      Th2-dominant adjuvant, whereas polyriboinosinic polyribocytidylic acid, a 
      Th1-inducer, enhanced splenocyte secretion of IFN-gamma without changing disease 
      incidence. These observations demonstrate that DCs efficiently present the TSHR 
      to naive T cells to induce TSHR antibodies and Graves'-like hyperthyroidism in 
      mice. In addition, our results challenge the previous concept of Th2 dominance in 
      Graves' hyperthyroidism and provide support for the role of Th1 immune response 
      in disease pathogenesis.
FAU - Kita-Furuyama, M
AU  - Kita-Furuyama M
AD  - First Department of Internal Medicine and Department of Pharmacology 1, Nagasaki 
      University School of Medicine, Nagasaki, Japan.
FAU - Nagayama, Y
AU  - Nagayama Y
FAU - Pichurin, P
AU  - Pichurin P
FAU - McLachlan, S M
AU  - McLachlan SM
FAU - Rapoport, B
AU  - Rapoport B
FAU - Eguchi, K
AU  - Eguchi K
LA  - eng
PT  - Journal Article
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (Autoantibodies)
RN  - 0 (Autoantigens)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Receptors, Thyrotropin)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adenoviridae/metabolism
MH  - Animals
MH  - Autoantibodies/biosynthesis
MH  - Autoantigens/*immunology
MH  - Dendritic Cells/*immunology
MH  - Female
MH  - Graves Disease/*immunology
MH  - Immunization/methods
MH  - Immunoglobulin G/biosynthesis
MH  - Interferon-gamma/biosynthesis
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Receptors, Thyrotropin/*immunology
MH  - Spleen/immunology
MH  - Th1 Cells/immunology
MH  - Th2 Cells/immunology
PMC - PMC1808615
EDAT- 2003/02/04 04:00
MHDA- 2003/04/08 05:00
PMCR- 2004/02/01
CRDT- 2003/02/04 04:00
PHST- 2003/02/04 04:00 [pubmed]
PHST- 2003/04/08 05:00 [medline]
PHST- 2003/02/04 04:00 [entrez]
PHST- 2004/02/01 00:00 [pmc-release]
AID - 2080 [pii]
AID - 10.1046/j.1365-2249.2003.02080.x [doi]
PST - ppublish
SO  - Clin Exp Immunol. 2003 Feb;131(2):234-40. doi: 10.1046/j.1365-2249.2003.02080.x.