Abstract
Previously we have found that T cells contribute to age-related glucose intolerance. The purpose of this study was to test the hypothesis that early life thymectomy at 3wks of age induces T cell aging and subsequent impairments in glucose homeostasis in otherwise young animals. Male C57BL6 mice underwent thymectomy (thymex; n=7) or sham surgery (control; n=7) at 3wks of age. A glucose (2g/kg) tolerance test (GTT) was performed at 6 and 9mo via intraperitoneal injection. Following euthanasia at 9mo of age, splenic T cell phenotype was assessed by flow cytometry. Group differences were assessed by independent samples t-test or repeated measures ANOVA and Bonferroni post-hoc test. Data are presented as mean±SEM. At 6mo, the thymex animals had a significantly lower fasting glucose compared to controls (156.8±7.9mg/dl,174.1±5.8mg/dl, p=0.06). During the GTT, 6mo old thymex mice had a greater area under the curve (AUC) compared to controls (31893.8±612.3mg/dl, 28020.9±1112.9mg/dl, p=0.03). At 9mo, the thymex mice had greater fasting glucose compared to controls (215.6±11.6mg/dl, 176.3±7.9mg/dl, p=0.016), as well as a greater GTT AUC (61445.4±1949.2mg/dl, 41527.5±2530.3mg/dl, p=0.0001). The thymex group also had increased fasting and glucose stimulated insulin levels compared to controls (0=1.3±0.2ng/ml 0.3±0.1ng/ml, p=0.01; 15=1.7±0.2ng/ml,0.44±0.1ng/ml, p=0.0014). Thymex mice exhibited a blunted splenic CD4:CD8 ratio (0.5±0.2, 1.1±0.2, p=0.04) compared to controls and a trend toward a memory CD8+ T cell phenotype (23.1±11.6%, 7.1±2.6, p=0.08), both consistent with aging. This data indicates that early life thymectomy may accelerate T cell aging, resulting in impairments in glucose tolerance in otherwise young and middle aged mice.