RGD Reference Report - Altered phenotype and function of dendritic cells in children with type 1 diabetes. - Rat Genome Database

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Altered phenotype and function of dendritic cells in children with type 1 diabetes.

Authors: Angelini, F  Del Duca, E  Piccinini, S  Pacciani, V  Rossi, P  Manca Bitti, ML 
Citation: Angelini F, etal., Clin Exp Immunol. 2005 Nov;142(2):341-6.
RGD ID: 2313911
Pubmed: PMID:16232222   (View Abstract at PubMed)
PMCID: PMC1809519   (View Article at PubMed Central)
DOI: DOI:10.1111/j.1365-2249.2005.02916.x   (Journal Full-text)

The importance of dendritic cells (DC) in the activation of T cells and in the maintenance of self-tolerance is well known. We investigated whether alterations in phenotype and function of DC may contribute to the pathogenesis of Type 1 diabetes (T1DM). Mature DC (mDC) from 18 children with T1DM and 10 age-matched healthy children were tested. mDC, derived from peripheral blood monocytes cultured for 6 days in presence of interleukin (IL)-4 and granulocyte-macrophage colony stimulating factor (GM-CSF) and stimulated with lipopolysaccharide (LPS) for the last 24 h, were phenotyped for the expression of the co-stimulatory molecules B7.1 and B7.2. In six patients and six controls allogenic mixed leucocyte reaction (AMLR) was performed using mDC and cord blood-derived naive T cells at a DC/T naive ratio of 1 : 200. Proliferation was assessed on day 7 by [(3)H]-thymidine incorporation assay. Mature DC derived from patients showed, compared with controls, a reduced expression of B7.1 [mean of fluorescence intensity (MFI): 36.2 +/- 14.3 versus 72.9 +/- 34.5; P = 0.004] and B7.2 (MFI: 122.7 +/- 67.5 versus 259.6 +/- 154.1; P = 0.02). We did not find differences in the HLA-DR expression (P = 0.07). Moreover, proliferative response of allogenic naive T cells cultured with mDC was impaired in the patients (13471 +/- 9917.2 versus 40976 +/- 24527.2 cpm, P = 0.04). We also measured IL-10 and IL-12 concentration in the supernatant of DC cultures. Interestingly, we observed in the patients a sevenfold higher level of IL-10 (P = 0.07) and a ninefold lower level of IL-12 (P = 0.01). Our data show a defect in the expression of the co-stimulatory molecules and an impairment of DC priming function, events that might contribute to T1DM pathogenesis.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CD86Humantype 1 diabetes mellitus  IEP protein:decreased expression:dendritic cellRGD 
Cd86Rattype 1 diabetes mellitus  ISOCD86 (Homo sapiens)protein:decreased expression:dendritic cellRGD 
Cd86Mousetype 1 diabetes mellitus  ISOCD86 (Homo sapiens)protein:decreased expression:dendritic cellRGD 

Objects Annotated

Genes (Rattus norvegicus)
Cd86  (CD86 molecule)

Genes (Mus musculus)
Cd86  (CD86 antigen)

Genes (Homo sapiens)
CD86  (CD86 molecule)


Additional Information