Fig. 4.

Sleep enhances the hepatitis A virus (HAV)-specific T helper (Th) cell response to vaccination which is strongly predicted by EEG slow wave activity during slow wave sleep (SWS) and associated release of immune regulatory hormones during early SWS-rich sleep. a Emergence of CD40L⁺ HAV-specific Th cells (percentage of total Th cells) after HAV vaccination (three shots at weeks 0, 8 and 16—vertical syringes) in two groups of subjects who either slept (black circle, thick line) or stayed awake (white circle, thin line) in the night following inoculations. y-axis log transformed. Means ± SEM are indicated. n = 12–27 for both groups. **p < 0.01, *p < 0.05, (*)p < 0.1 for comparisons between sleep and wake conditions. b Scatter plots of the correlations between slow wave activity (averaged across the three post-inoculation nights) and the frequency of CD40L⁺ HAV-specific Th cells (percentage of total Th cells) at weeks 18–20 (left panel) and week 52 (right panel). c Correlation coefficients between average GH, prolactin and cortisol concentrations during the early, SWS-rich part (0:30–2:00 a.m.) of post-inoculation nights and frequency of HAV-specific Th cells at weeks 8, 12, 16, 18 and 20 and 1 year after HAV vaccination. (Analyses performed across sleep and wake groups.) Note the most robust correlations for an ‘Adjuvant Factor’ describing the synergistic action of the three hormones of interest by the formula GH × prolactin/cortisol. ***p < 0.001, **p < 0.01, *p < 0.05. Modified from Lange et al. [75]