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.
Angelini, F., Del Duca, E., Piccinini, S., Pacciani, V., Rossi, P., & Manca Bitti, M. (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., Del Duca, E., Piccinini, S., Pacciani, V., Rossi, P., & Manca Bitti, M. (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):||Esperti anonimi|
|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; Manca Bitti, M|
|Appare nelle tipologie:||01 - Articolo su rivista|