Investigating markers of T-Cell activation due to chronic inflammation in Type 2 Diabetes.

Abstract

Background: Type 2 diabetes (T2D) is amongst the leading causes of mortality associated with non-communicable diseases. Insulin resistance, low-grade chronic inflammation, together with T cell activation, play an essential role in the pathogenesis of T2D and cardiovascular diseases. However, the role of T cells in the pathogenesis of T2D remains unclear. Study Design and Methods: Thirty-four (n = 34) male C57BL/6 mice were obtained from the UKZN, Biomedical Resource Unit in Westville. The mice were randomized into a six-week low-fat diet (LFD) fed control group and a high-fat diet (HFD) fed experimental group. Body weights, plasma, glucose levels, T cell activation, and exhaustion markers were compared amongst the two groups before and post-treatment with either low dose aspirin (LDA), a combination of low-dose aspirin and metformin or Clopidogrel. Results: HFD-fed mice demonstrated weight gain, elevated plasma glucose (p = 0.008), and insulin levels (p=0.026) within two weeks of consuming the diet. CD69 expression levels on T cells were lower in the HFD-fed group when compared to the LFD-fed group (p = 0.0208). All the treated groups demonstrated elevated levels of CD69 expression on T cells. Only the LDA treated group showed a tendency towards a reduction in PD-1 levels of expression on T cells when compared to the untreated HFD-fed group (p = 0.0711). Discussion: Impaired glucose tolerance is associated with increased T cell activation in prediabetes. The HFD fed mice had reduced levels of CD69 expression on T cells, indicating T cell activation and chronic inflammation. CD69 modulates T cell egress to inflamed tissue. Expression levels of CD69 in T cells was ameliorated post-treatment with LDA, a combination of LDA and metformin or Clopidogrel, therefore preventing cardiovascular complications. Conclusion: T cell-mediated inflammatory responses can be attenuate by treatment with LDA, a combination of LDA and metformin or Clopidogrel in T2D. Increased T cell activation markers in hyperglycemic conditions demonstrated that chronic activation of T cells poses a risk to develop T cell dysfunction and T2D. Therefore, more focus should be given to the chronic activation of T cells in order to prevent the development of T2D rather than only focusing on obesity as a potential predisposing factor.