Impaired yield, phenotype, and function of monocyte-derived dendritic cells in humans at risk for insulin-dependent diabetes
- Author(s)
- Takahashi, K; Honeyman, MC; Harrison, LC;
- Details
- Publication Year 1998-09-01,Volume 161,Issue #5,Page 2629-2635
- Journal Title
- JOURNAL OF IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- Dendritic cells (DC) present Ag to naive T cells and are therefore pivotal in shaping immune responses. DC may either immunize or tolerize T cells. Humans with pancreatic islet autoimmunity at high risk for insulin-dependent diabetes mellitus (IDDM) present the opportunity to investigate DC in autoimmune disease. We compared DC phenotype and function in 12 euglycemic, asymptomatic IDDM relatives with islet autoimmunity and controls matched for age, sex, and MHC class II alleles, DC were generated from adherent peripheral blood cells by culture with granulocyte/macrophage- CSF and IL-4. The yield of DC was significantly lower in IDDM relatives than in controls, While the DC phenotype, HLA-DR(+)CD14(-), was expressed by greater than or equal to 90% of the cells generated from relatives and controls, the proportion of cells that expressed CD1a and the costimulator molecules CD80 (B7-1) and CD86(B7-2) was significantly lower in IDDM relatives. In addition, B7-1 and B7-2 expression per cell was significantly lower in IDDM relatives, These phenotypic changes were accompanied by reduced stimulation of autologous CD4 cells by DC from IDDM relatives. Similar findings were obtained in three recently diagnosed IDDM patients. These findings indicate that impairment of DC phenotype and function is a marker of islet autoimmunity and are consistent with a role for impaired DC function in the pathogenesis of autoimmune disease.
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Keywords
- MIXED LYMPHOCYTE-REACTION; GLUTAMIC-ACID DECARBOXYLASE; COLONY-STIMULATING FACTOR; ANTIGEN-PRESENTING CELLS; T-CELLS; CYTOKINE PRODUCTION; IMMUNE-RESPONSE; HUMAN BLOOD; NOD MOUSE; IN-VIVO
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Creation Date: 1998-09-01 12:00:00