Persistent activation of T cells perturbs neurotransmitter production in the brain


T cells, a subset of white blood cells, are of key importance to the body's immune response to infection and disease. Although it's known that activated T cells reorganize their metabolism to perform their function, the systemic effect of persistent T-cell activation has not been well defined.

To address this, a team composed of researchers from Japan and China used mice lacking an inhibitory regulator of T-cell activity. They found that persistent activation of T cells resulted in a systemic metabolomic change and ultimately led to behavior changes.

T-cell response is regulated by a range of molecules, including programmed death-1 (PD-1). PD-1 plays a key role in suppressing T-cell activity. To investigate the systemic effect of sustained activation of T cells, the team generated mice that lacked PD-1. Working with the PD-1-deficient mice, the team discovered that the building blocks of proteins, amino acids (AAs), accumulated in activated T cells in the lymph nodes, leading to the depletion of AAs in the blood.

Further, the systemic decrease in two particular AAs, tryptophan and tyrosine, caused the brain to produce smaller amounts of serotonin and dopamine, which are both neurotransmitters critical for normal brain function. The team observed that the deficiency in serotonin and dopamine led to behavioral changes in the PD-1-deficient mice, such as anxiety-like behavior and exacerbated fear responses.

Serotonin takes control of our moods, sleep, appetite, learning ability, and many other brain functions. Serotonin has been linked with depression and several other disorders. Dopamine also has several distinct roles in the body, one of which is in the reward system. Abnormalities in the dopamine system correlate with different medical conditions such as Parkinson's disease, schizophrenia, and addiction.

Collectively, the data shed light on how excessive T cell activation could cause systemic effects. The study would have significant implications for the research of autoimmune conditions involving overactivation of T cells as well as mental disorders like depression.

You can read the full paper "Metabolic shift induced by systemic activation of T cells in PD-1-deficient mice perturbs brain monoamines and emotional behavior" in Nature Immunology.
 
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