Sleep Regulates Activation Of Antigen-specific T Cells

A new study helps explain how sleep can fight off an infection, whereas other conditions, such as chronic stress, can make the body more susceptible to illness. The work was led by Stoyan Dimitrov and Luciana Besedovsky at the University of Tübingen in Germany.

T-cells are a type of white blood cell that are critical to the body’s immune response. When T cells recognize a specific target, such as a cell infected with a virus, they activate sticky proteins known as integrins that allow them to attach to their target and, in the case of a virally infected cell, kill it.

While much is known about the signals that activate integrins, signals that might dampen the ability of T cells to attach to their targets are less well understood.

Gαs-coupled Receptor Agonists

Dimitrov and colleagues decided to investigate the effects of a diverse group of signaling molecules known as Gαs-coupled receptor agonists. Many of these molecules can suppress the immune system, but whether they inhibit the ability of T cells to activate their integrins and attach to target cells was unknown.

They found that certain Gαs-coupled receptor agonists, including the hormones adrenaline and noradrenaline, the proinflammatory molecules prostaglandin E2 and D2, and the neuromodulator adenosine, prevented T cells from activating their integrins after recognizing their target.

“The levels of these molecules needed to inhibit integrin activation are observed in many pathological conditions, such as tumor growth, malaria infection, hypoxia, and stress. This pathway may therefore contribute to the immune suppression associated with these pathologies,”

says Dimitrov.

Integrin Activation

Adrenaline and prostaglandin levels dip while the body is asleep. Dimitrov and colleagues compared T cells taken from healthy volunteers while they slept or stayed awake all night.

T cells taken from sleeping volunteers showed significantly higher levels of integrin activation than T cells taken from wakeful subjects.

sleep regulates integrin activation

Credit: Dimitrov et al. CC-BY

The researchers were able to confirm that the beneficial effect of sleep on T cell integrin activation was due to the decrease in Gαs-coupled receptor activation.

“Our findings show that sleep has the potential to enhance the efficiency of T cell responses, which is especially relevant in light of the high prevalence of sleep disorders and conditions characterized by impaired sleep, such as depression, chronic stress, aging, and shift work,”

says author Luciana Besedovsky.

In addition to helping explain the beneficial effects of sleep and the negative effects of conditions such as stress, Dimitrov and colleagues’ study could spur the development of new therapeutic strategies that improve the ability of T cells to attach to their targets. This could be useful, for example, for cancer immunotherapy, where T-cells are prompted to attack and kill tumor cells.

Stoyan Dimitrov, Tanja Lange, Cécile Gouttefangeas, Anja T.R. Jensen, Michael Szczepanski, Jannik Lehnnolz, Surjo Soekadar, Hans-Georg Rammensee, Jan Born, Luciana Besedovsky
Gαs-coupled receptor signaling and sleep regulate integrin activation of human antigen-specific T cells
Journal of Experimental Medicine Feb 2019, jem.20181169; DOI: 10.1084/jem.20181169

Top Image: Dimitrov et al. CC-BY