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 [H-3]-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.
Angelini F., D.D.E. (2005). Altered phenotype and function of dendritic cells in children with type 1 diabetes. CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 142(2), 341-346.
|Tipologia:||Articolo su rivista|
|Citazione:||Angelini F., D.D.E. (2005). Altered phenotype and function of dendritic cells in children with type 1 diabetes. CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 142(2), 341-346.|
|IF:||Con Impact Factor ISI|
|Settore Scientifico Disciplinare:||Settore MED/38 - Pediatria Generale e Specialistica|
|Revisione (peer review):||Sì, ma tipo non specificato|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1111/j.1365-2249.2005.02916.x|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||nov-2005|
|Titolo:||Altered phenotype and function of dendritic cells in children with type 1 diabetes|
|Autori:||Angelini F., Del Duca E., Piccinini S., Pacciani V., Rossi P., Bitti M.L.M.|
|Appare nelle tipologie:||01 - Articolo su rivista|