Dendritic Cells and Scavenger Macrophages in Pancreatic Islets of Prediabetic BB Rats

Abstract

Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease whose notorious pathologic feature is insulitis accompanied by destruction of beta-cells. In this morphological study, we examined the pancreatic events during the onset of diabetes in spontaneously diabetic BB/Organon rats. Dendritic cells were the first cells to accumulate around the islets, followed by lymphocytes. Scavenger macrophages and MHC class II-positive beta-cells were only seen late in the disease. These observations suggest a role for antigen-presenting dendritic cells in the onset of the beta-cell-specific autoimmune reaction and emphasize the necessity to distinguish between the several monocyte-macrophage subtypes in studies on the pathogenesis of IDDM.

Developing dendritic cells become ‘lacy’ cells packed with fat and glycogen

“…Oxidized low-density lipoprotein (LDL) can also promote the maturation of DCs from monocyte precursors and causes the down-regulation of interleukin (IL)-12 production in DCs. [11][12][13] DCs are also early participants in developing diabetic lesions before the appearance of scavenger macrophages, 14 and DCs are present in atherosclerotic arteries. 15 To test the hypothesis that DCs may acquire fat and glycogen stores during development, we studied DCs developing from mouse bone marrow stem cells with and without increasing doses of IL-4 or lipopolysaccharide (LPS), both of which promote the stimulatory ability of DCs for T cells.…”

Quantitative phenotypic and functional analyses of islet immune cells before and after diabetes onset in the BB rat

“…These considerations indicate the need for functional data to be performed in the key in situ subsets observed (see below.) T cells are described as the major cell type in islets during the later stages of inflammation [1,3,4,7]. When phenotyping splenic T cells in BB rats, we noted a population of CD5-, TCR alpha/beta + T cells [8].…”

“…Using semiquantitative methods such as immunohistochemistry of pancreas tissue, several immune cell types have been described to spontaneously occur in the diabetic-prone BB rat islets or pancreas [1][2][3][4][5][6][7]. The in situ islet infiltration of specific cell types is time-dependent [1,5,6].…”

“…The in situ islet infiltration of specific cell types is time-dependent [1,5,6]. Early infiltrating cells in this process are dendritic cells and macrophage, followed by T cells, natural killer (NK) cells and later by B lymphocytes [1,[4][5][6][7]. These semiquantitative analyses suggest that just prior to or after diabetes onset, the relative percentages of in situ islet mononuclear cells follow the hierarchy of dendritic cell/macrophage, CD4+T cells, similar or lesser numbers of CD8 § T cells, and finally NK cells [3][4][5][6][7].…”

“…Early infiltrating cells in this process are dendritic cells and macrophage, followed by T cells, natural killer (NK) cells and later by B lymphocytes [1,[4][5][6][7]. These semiquantitative analyses suggest that just prior to or after diabetes onset, the relative percentages of in situ islet mononuclear cells follow the hierarchy of dendritic cell/macrophage, CD4+T cells, similar or lesser numbers of CD8 § T cells, and finally NK cells [3][4][5][6][7]. Activated T cells are also suggested to be present in the BB * This work was reported in part at the European Association for the Study of Diabetes in Copenhagen, Denmark, in September, 1990 and at the International Diabetes Federation Congress in Washington DC, June, 1991 rat pancreas or islets [2,3].…”