TY - JOUR
T1 - Altered phenotype and function of dendritic cells in children with type 1 diabetes
AU - Angelini, Federica
AU - Del Duca, E.
AU - Piccinini, S.
AU - Pacciani, V.
AU - Rossi, P.
AU - Bitti, M. L Manca
PY - 2005/11
Y1 - 2005/11
N2 - 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.
AB - 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.
KW - B7.1/ B7.2
KW - Dendritic cells
KW - Type 1 diabetes
UR - http://www.scopus.com/inward/record.url?scp=27644491043&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=27644491043&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2249.2005.02916.x
DO - 10.1111/j.1365-2249.2005.02916.x
M3 - Article
C2 - 16232222
AN - SCOPUS:27644491043
VL - 142
SP - 341
EP - 346
JO - Clinical and Experimental Immunology
JF - Clinical and Experimental Immunology
SN - 0009-9104
IS - 2
ER -