Naturally Diabetic NHP Immune Cell Changes Correspond to Human Type 2 Diabetes
While changes in immune cell distribution have been shown to correlate with disease progression in human type 2 diabetes, similar studies have not been carried out in spontaneously diabetic NHPs, which are highly translatable preclinical models for diabetes and other metabolic diseases.
At the 77th Scientific Sessions of the American Diabetes Association, we presented our data evaluating the distribution of individual immune cells in diabetic NHPs and how this correlated to the progression of diabetes in this model. You can now review our video poster, with full transcript below.
Hello, this is Judith Gorski, Global Director, Scientific Engagement, Crown Bioscience. Thank you for joining me today as I walk through our poster titled ‘The Depletion of Peripheral NK Cells and NK-T Lymphocytes in a Spontaneously Diabetic Non-Human Primate Model’.
Spontaneously Diabetic NHPs – A Valuable Translational Resource
The spontaneously diabetic cynomolgus monkey shown in Figure 1 has been recognized as a highly translatable model for the evaluation of potential therapeutics in the treatment of metabolic diseases, such as diabetes, obesity, and hyperlipidemia.
Immune Cell Changes Correlate with Disease Progression in Human Type 2 Diabetes
In the human type 2 diabetic patient, there are changes in immune cell distribution that have been found to correlate with disease progression. As such NK cell numbers were found to be lower in diabetic patients while CD4 positive T cells and total lymphocytes were actually not affected.
The aim of this study was to examine changes in immune cell distribution in the spontaneously diabetic cynomolgus monkeys.
We used male, diabetic and normoglycemic cynomolgus macaques. These animals were selected based on their fasting blood glucose and insulin levels, shown in Table 1. The average age for the control animals was 16 and the average age for the diabetic animals was 18 years of age. Body weights were no different, but as you can see blood glucose and HbA1c values were significantly different between the groups.
Lower Frequencies of NK and NK-T Cells, but not CD4+ T Cells, in Diabetic NHPs
Following an overnight fast, isolated plasma was immediately processed before FACS analysis, using antibodies against different immune cell surface markers, shown here in Table 2. Different immune cell types were identified by gating cell populations with signals from the antibodies.
In Figure 2 we found that there were lower frequencies of NK and NK-T cells in the diabetic monkeys in gold versus the control monkeys in blue. In contrast, we found that while the CD4 positive T cell levels were actually not different between the groups.
Plasma NK and NK-T Cells Correlate Negatively with Fasting Blood Glucose
In Figure 4 we show the correlations of NK cells and NK-T cells versus fasted blood glucose levels. The number of the plasma NK and NK-T cells correlated negatively with the fasting blood glucose levels in cynomolgus monkeys. Neither NK or NK-T cells were correlated with animal age, body weight, waist circumference, serum insulin, or CRP levels. These findings were consistent with the observations for type 2 diabetic patients.
Useful Model for Evaluating Drugs which Modulate Specific Immune Cells
In conclusion, spontaneously diabetic cyno macaques display changes in peripheral immune cell frequencies very similar to those observed in type 2 diabetic patients. Furthermore, we provide strong evidence that this animal model is an excellent tool for diabetic or related metabolic research with the possibility of its extended usage in the development of drug candidates that might modulate specific immune cell populations.