Accumulation of γδ T cells in visceral fat with aging promotes chronic inflammation.

Adipose tissue dysfunction is strongly linked to the development of chronic inflammation and cardiometabolic disorders in aging. While much attention has been given to the role of resident adipose tissue immune cells in the disruption of homeostasis in obesity, age-specific effects remain understudied. Here, we identified and characterized a population of γδ T cells, which show unique age-dependent accumulation in the visceral adipose tissue (VAT) of both mice and humans. Diet-induced obesity likewise increased γδ T cell numbers; however, the effect was greater in the aged where the increase was independent of fat mass. γδ T cells in VAT express a tissue-resident memory T cell phenotype (CD44hiCD62LlowCD69+) and are predominantly IL-17A-producing cells. Transcriptome analyses of immunomagnetically purified γδ T cells identified significant age-associated differences in expression of genes related to inflammation, immune cell composition, and adipocyte differentiation, suggesting age-dependent qualitative changes in addition to the quantitative increase. Genetic deficiency of γδ T cells in old age improved the metabolic phenotype, characterized by increased respiratory exchange ratio, and lowered levels of IL-6 both systemically and locally in VAT. Decreased IL-6 was predominantly due to reduced production by non-immune stromal cells, primarily preadipocytes, and adipose-derived stem cells. Collectively, these findings suggest that an age-dependent increase of tissue-resident γδ T cells in VAT contributes to local and systemic chronic inflammation and metabolic dysfunction in aging.

Usefulness of Findings by Multimodality Imaging to Stratify Risk of Major Adverse Cardiac Events After Sepsis at 1 and 12 months.

Cardiovascular complications are reported in up to 30% of sepsis survivors. Currently, there is limited evidence to guide cardiovascular risk stratification of septic patients. We propose the use of left ventricular ejection fraction (LVEF) and coronary artery calcification (CAC) on nongated computed tomography (CT) scans to identify septic patients at highest risk for major adverse cardiovascular events (MACE). We retrospectively reviewed 517 adult patients with sepsis, elevated troponin levels, nongated CT scans that visualized the coronaries, and an echocardiogram. Patients were stratified into 4 groups based on the LVEF and presence or absence of CAC. Using the CAC negative/LVEF ≥ 50% as a control, we compared MACE and all-cause mortality outcomes across the patient groups. At 30 days, 39 patients (7.5%) experienced MACE and 166 patients (32%) died. Patients with no CAC and LVEF ≥ 50% experienced no MACE at 30 days or 1 year. Among patients with EF < 50%, CAC positive or negative patients were statistically more likely to experience a MACE event at 30 days (p < 0.001 for both groups). After 30 days, a further 6 patients (1.2%) experienced MACE and 66 (12.7%) patients died within the first year. Patients with CAC positive/LVEF < 50% experienced the highest rates of MACE at 1 year (p < 0.001). In conclusion, the combination of LVEF on echocardiography and CAC on nongated CT scans provides a powerful risk stratification tool for predicting cardiovascular events in septic patients.