Reduced frequency of peripheral plasmacytoid dendritic cells in type 1 diabetes.

Dendritic cells (DCs) as antigen presenting cells play an important role in the initiation of an autoimmune disease like type 1 diabetes. Although there is evidence from the NOD mouse model that the function and frequency of DCs is altered in type 1 diabetes, there is little data on dendritic cells in human type 1 diabetes. We investigated peripheral blood myeloid (mDC1 and mDC2) and plasmacytoid dendritic cells (pDCs) in 15 type 1 diabetes patients with recent onset (within the last 3 months) of type 1 diabetes as well as in 15 patients with long standing (more than 5 years) type 1 diabetes by flow cytometry. Both groups were compared to age matched controls. We observed a significantly reduced percentage of pDCs of peripheral blood mononuclear cells (PBMCs) in both recent onset (0.13 vs. 0.25%, p=0.01) and long standing type 1 diabetes patients (0.13 vs. 0.24%, p=0.01). The absolute counts of pDCs per ml of blood were also significantly lower in both recent onset (mean 9560 vs. 13524, p=0.048) and long-standing diabetes (mean 7869 vs. 12202; p=0.05). The percentage of mDC1 was significantly diminished in recent onset (0.21% vs. 0.30%, p=0.034), but not in long standing type 1 diabetes. Our study demonstrates a persisting reduction of peripheral plasmacytoid DCs in type 1 diabetes patients. Since pDCs are involved in the control of immune responses and inducing regulatory cells, a reduced number of pDCs may predispose to an autoimmune reaction in the pancreatic islets.

Reduced frequency of peripheral dendritic cells in type 2 diabetes.

OBJECTIVE: It is a common clinical experience that type 2 diabetic patients are susceptible to opportunistic infections. The underlying reasons for this immune deficiency are not yet understood. Dendritic cells (DC) play a key role in initiating innate and adapted immune responses. DESIGN: In order to investigate changes in the DC compartment in the peripheral blood in type 2 diabetes, we analyzed blood from patients under poor and good metabolic control and compared them to healthy controls. PATIENTS: 5 mls of blood were collected from 15 healthy controls, 15 diabetic patients with an HbA1c <7.0 and 15 patients with an HbA1c >9.5%. Age range was 44-80 years. Patients were age-matched with the control group. MEASUREMENT: Blood DC were enumerated by flow cytometry after staining with antibodies against the blood dendritic cells antigens 1-3 (BDCA 1-3). This allows quantification of the DC subtypes: myeloid dendritic cells type 1 (mDC1, mDC2) and plasmacytoid dendritic cells (pDC). RESULTS: The relative and absolute frequency for both mDC1 and pDC was clearly diminished in patients with poor metabolic control as compared to healthy controls. In patients with good metabolic control the reduction of DC was less pronounced but still significant, particularly for mDC1. CONCLUSION: Hyperglycemic metabolism does affect the pool of peripheral DCs and leads to a reduction of both, mDC1 and pDC. Even patients considered to be under good metabolic control appear to have a reduced peripheral pool of DC.