IL-17 and IFN-γ Productions by CD4+ T cells and T cell Subsets Expressing NKG2D Associated with the Number of Risk Factors for Cardiovascular Diseases

Mol Immunol. 2020 May 6:122:193-199. doi: 10.1016/j.molimm.2020.04.003. Online ahead of print.

Abstract

Cardiovascular diseases (CVD), which are major causes of morbidity and mortality worldwide, are characterized by complicated chronic inflammatory manifestation inducing from multi-risk factors. Previously, we have identified a pathological T cell subpopulation producing interleukin (IL)-17 in diabetes. We hypothesized that this T cell subpopulation could exist in the elderly with persistence low grade inflammation related to the risk factors for cardiovascular diseases. Thus, we investigated whether high levels of the natural group 2, member D (NKG2D) expression, IL-17 and interferon (IFN)-γ production by CD4 + T cells and T cell subsets were more prevalent in individuals who had age ≥ 60 years with > 2 risk factors for CVD (dyslipidemia, hypertension and/or diabetes mellitus) compared to subjects who had < 2 risk factors. Using flow cytometric analysis, we found that CD4 + T cells of subjects who had ≥ 2 risk factors had significantly higher NKG2D expression than those of subjects with < 2 risk factors (P = 0.023). Apparently, CD4+CD28null T subset of both two groups preferentially expressed NKG2D, and prominently produced IL-17 and IFN-γ compared to the CD4+CD28+ T subset. Expectedly, there was a statistical significance of IL-17 and IFN-γ production of CD4 + 28nullNKG2D + T cells (P = 0.037 and P = 0.042, respectively). We concluded that cumulative number of CVD risk factors associated with progressive alteration of CD4+ T cell phenotypes and their functions. Handling of metabolic risk factors may be an approach for healthcare of the elderly to prevent cardiovascular morbidity resulting from alteration of immunity.

Keywords: CD4+T subsets; IFN-γ; IL-17; NKG2D; cardiovascular diseases risk factors.