Calorie restriction enhances T-cell-mediated immune response in adult overweight men and women

Abstract

Calorie restriction (CR) enhances immune response and prolongs life span in animals. However, information on the applicability of these results to humans is limited. T-cell function declines with age. We examined effects of CR on T-cell function in humans. Forty-six overweight, nonobese participants aged 20-42 years were randomly assigned to 30% or 10% CR group for 6 months. Delayed-type hypersensitivity (DTH), T-cell proliferation (TP), and prostaglandin E(2) (PGE(2)) productions were determined before and after CR. DTH and TP to T-cell mitogens were increased in both groups over baseline (p < or = .019). However, number of positive responses to DTH antigens (p = .016) and TP to anti-CD3 reached statistical significance only after 30% CR (p = .001). Lipopolysaccharide-stimulated PGE(2) was reduced in both groups but reached statistical significance after 30% CR (p < or = .029). These results, for the first time, show that 6-month CR in humans improves T-cell function.

Figure 1.

Effect of calorie restriction (CR) on delayed-type hypersensitivity (DTH) in humans. Participants were administered a Mantoux test with three recall antigens and a control at baseline (M0) and following 6 months (M6) of 10% (A) or 30% (B) CR as described in the Methods section. The response of the two CR groups combined is represented in (C). Data are mean ± standard error of the mean of the diameter of induration measured at 24 hours, 48 hours, or the maximum response of the two time points. N = 12 for the 10% and 34 for the 30% group and 46 for the combined group. **p = .01–.001 and ***p < .001 for differences of DTH responses between the baseline and after 6-month CR with Wilcoxon signed rank tests.

Figure 2.

Effect of 10% and 30% calorie restriction (CR) on lymphocyte proliferation. Fasting whole blood was stimulated by mitogens 25 μg/mL concanavalin A (Con A) (A), 25 μg/mL phytohemagglutinin A (B), or 0.1 μg/mL anti-CD3 (C) for 72 hours, and proliferation was measured by [³H]-thymidine incorporation as described in the Methods section. *p ≤ .05–.01, **p = .01–.001, and ***p < .001 for differences of lymphocyte proliferation between the baseline (M0) and after 6-month (M6) CR by Wilcoxon signed rank tests.

Figure 3.

Effect of 10% and 30% calorie restriction (CR) on LPS-stimulated prostaglandin E₂ (PGE₂) production. Whole blood was stimulated with 1 μg/mL LPS for 48 hours. PGE₂ in supernatant was measured as described in the Methods section. *p = .05–.01 and ns = nonsignificant for differences of PGE₂ production between the baseline (M0) and after 6-month (M6) CR with Wilcoxon signed rank tests.

Figure 4.

Correlation between calorie restriction (CR)–induced percent changes in body mass index (BMI) in relation to percent changes of concanavalin A (Con A) response (A) and percent changes of phytohemagglutinin A (PHA) response (B). The p values were determined using Spearman correlation tests.