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 [10.1111/j.1365-2249.2005.02916.x].

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

ANGELINI, FEDERICA;ROSSI, PAOLO;
2005-11

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 [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.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/38 - Pediatria Generale e Specialistica
eng
Con Impact Factor ISI
B7.1/ B7.2; Dendritic cells; Type 1 diabetes
B7 antigen; CD86 antigen; granulocyte macrophage colony stimulating factor; HLA DR antigen; interleukin 10; interleukin 12; interleukin 4; lipopolysaccharide; thymidine; tritium; adolescent; age distribution; article; blood cell; cell culture; cell function; cell maturation; cell proliferation; cell stimulation; child; clinical article; concentration (parameters); controlled study; dendritic cell; DNA synthesis; female; fluorescence; health status; human; human cell; immunity; infant; insulin dependent diabetes mellitus; male; molecule; monocyte; pathogenesis; pediatrics; phenotype; priority journal; protein expression; supernatant; T lymphocyte; time; umbilical cord blood; Adolescent; Antigens, CD80; Antigens, CD86; Cells, Cultured; Child; Child, Preschool; Dendritic Cells; Diabetes Mellitus, Type 1; Female; Humans; Immunophenotyping; Infant; Interleukin-10; Interleukin-12; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Male; Self Tolerance; T-Lymphocytes
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 [10.1111/j.1365-2249.2005.02916.x].
Angelini, F; Del Duca, E; Piccinini, S; Pacciani, V; Rossi, P; Bitti, Mlm
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/57264
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