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

Federica Angelini, E. Del Duca, S. Piccinini, V. Pacciani, P. Rossi, M. L Manca Bitti

Research output: Contribution to journalArticlepeer-review

Abstract

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 [3H]-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.

Original languageEnglish
Pages (from-to)341-346
Number of pages6
JournalClinical and Experimental Immunology
Volume142
Issue number2
DOIs
Publication statusPublished - Nov 2005

Keywords

  • B7.1/ B7.2
  • Dendritic cells
  • Type 1 diabetes

ASJC Scopus subject areas

  • Immunology

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