Catching Arterial Aging: Preliminary Evidence of Autoantigen Specific T Cell Activation in Aging Arteries

Cardiovascular disease (CVD) is the leading cause of death in the United States, and aging is a major risk factor for the development of CVD. Aging is associated with vascular inflammation and T cell accumulation, even in the absence of infection or injury. Previous studies in rodent models of hypertension and heart failure suggest that autoantigens may contribute to cardiovascular dysfunction. However, whether autoantigens inappropriately activate T cells in old mice and drive age related arterial dysfunction is unclear. PURPOSE: This study aimed to determine whether age related arterial inflammation results from antigen dependent activation, suggesting the presence of autoantigens in the aging arteries. METHODS: Aortas from young (4-6mo) and old (22-24mo) RAG-/- mice were harvested, sectioned for histology, and incubated with FBS or young or old sex-matched plasma from a C57BL/6 mouse. This tissue was then stained with a fluorescent conjugated IgG. Immunofluorescence was employed to detect antibody binding. Splenocytes from young C57BL/6 mice were stained with CFSE and incubated with either young or old mesenteric artery protein homogenate for 72 hours. The cells were then harvested and stained with anti-CD3, anti-CD44, and anti-CD69 antibodies and analyzed by flow cytometry. RESULTS: Immunofluorescence revealed greater IgG binding in aortic tissues incubated with old plasma, suggesting the presence of arterial antigens. Young splenocytes exposed to old homogenate exhibited significantly greater T cell activation and proliferation compared to young splenocytes incubated with young homogenate. CONCLUSION: These finding suggest that arterial antibodies exist in old mice and can promote T cell activation and proliferation. This suggests that T cell mediated arterial inflammation in aging may be driven by autoantigen immune responses.