Altered phenotype and function of dendritic cells in children with type 1 diabetes
| Autor: | M. L. Manca Bitti, F. Angelini, Valentina Pacciani, Paolo Rossi, Simona Piccinini, E. Del Duca |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Male
age distribution Lipopolysaccharide B7 antigen T-Lymphocytes Priming (immunology) cell maturation health status HLA DR antigen thymidine Lymphocyte Activation Pathogenesis chemistry.chemical_compound CD80 Clinical Studies T lymphocyte Immunology and Allergy CD86 Child time Cells Cultured clinical article Cultured tritium pathogenesis lipopolysaccharide article Interleukin Interleukin-12 Mixed Interleukin-10 B7.1/ B7.2 Type 1 diabetes Self Tolerance priority journal Child Preschool monocyte Antigens CD80 Dendritic Cells Humans Lymphocyte Culture Test Mixed Antigens CD86 Infant Diabetes Mellitus Type 1 Adolescent Immunophenotyping Female B7-1 Antigen fluorescence granulocyte macrophage colony stimulating factor Type 1 medicine.medical_specialty pediatrics dendritic cell phenotype Cells Immunology cell stimulation CD86 antigen interleukin 10 interleukin 12 interleukin 4 adolescent blood cell cell culture cell function cell proliferation child concentration (parameters) controlled study DNA synthesis female human human cell immunity infant insulin dependent diabetes mellitus male molecule protein expression supernatant umbilical cord blood Biology Internal medicine medicine Diabetes Mellitus Antigens Antigen-presenting cell Lymphocyte Culture Test Preschool Autoimmune disease Settore MED/38 - Pediatria Generale e Specialistica Dendritic cell medicine.disease Colony-stimulating factor Endocrinology chemistry Dendritic cells B7-2 Antigen |
| Popis: | SummaryThe 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|