title: Effects of sleep and sleep-related hormones on T-cell migration
Creators: name: Martínez Albert, Estefanía
Publisher: name: Universität Tübingen
Year: 2024
Subjects: subject: 570
subject: Sleep
subject: Adaptive immunity
subject: T-cell migration
subject: Growth hormone
subject: Prolactin
subject: Lymph node homing

description: Sleep is a fundamental aspect of human life, occupying approximately one-third of our time. Its importance in maintaining overall health and well-being is widely recognized, including its role in regulating the immune system. Experimental studies demonstrate that individuals who sleep after vaccination exhibit significantly enhanced antigen-specific antibody and T-cell responses compared to those who remain awake, emphasizing the impact of sleep on immune defense mechanisms. The mechanisms behind this effect of sleep are still unclear. Based on the consistent finding that sleep reduces T-cell numbers in the bloodstream, one hypothesis is that sleep fosters T-cell migration to lymph nodes (LNs), where immune responses are coordinated. The effects of sleep on the endocrine system may mediate the impact of sleep on immune functions. During sleep, hormonal changes occur, with high growth hormone (GH) and prolactin (PRL) levels promoting a pro-inflammatory environment conducive to immune activation and response. This dissertation aimed to investigate the role of sleep in T-cell migration to LNs, which is crucial for adaptive immune responses. The experiments conducted within the scope of this dissertation sought to measure the migration of several T-cell subsets during normal sleep and nocturnal wakefulness, focusing on the LN-homing chemokine CCL19. Additionally, a second aim was to understand the role of the sleep-regulated hormones GH and PRL in potentially mediating the effects of sleep on T-cell migration by conducting experiments employing hormone concentrations comparable to those occurring under sleep conditions. It was hypothesized that sleep induces stronger T-cell migration towards CCL19 mediated by the sleep-related hormones GH and PRL. To explore the effect of sleep on T-cell migration, three experiments were conducted within the context of this thesis. In Experiment I, participants underwent two 24-hour sessions in a sleep laboratory, with one session involving uninterrupted sleep and the other continuous wakefulness. Blood samples were collected regularly to assess T-cell counts and migration patterns. Sleep was found to decrease the total number of circulating T cells and several subsets. Sleep also selectively enhanced the migration of various T-cell subsets towards the LN-homing chemokine CCL19, without affecting migration towards CCL5, a chemokine involved in inflammation. Experiment II explored the influence of the sleep-associated hormones GH and PRL on T-cell migration, revealing that GH and PRL increased migration towards CCL19. Experiment III confirmed that plasma from sleeping individuals enhanced T-cell migration towards CCL19, and this effect was mitigated by blockers of GH and PRL. These findings suggest a role for GH and PRL in mediating the effects of sleep on T-cell behavior. Future research may delve into molecular pathways involved in these sleep effects, potentially identifying therapeutic targets for immune-related disorders. Translating these findings into clinical practice could lead to interventions aimed at improving sleep quality in individuals with compromised immune function, possibly improving patient outcomes and enhancing immune responses, particularly post-vaccination.