T cells are necessary for resolution of inflammation-induced depression-like behavior

Abstract

Depression is one of the most common mental disorders worldwide. Accumulating evidence indicates a role of the innate immune system in the onset of depression. However, how T cells contribute to depression is unknown. Recently, we showed that T cells are required for resolution of neuropathic pain. Here, we hypothesized that T cells are also required for resolution of inflammation-induced depression. We compared the duration of depression-like behavior of C57Bl/6 WT and T cell deficient (Rag1-/- and Rag2-/-) mice in response to lipopolysaccharide or complete Freund’s adjuvant. Depression-like behavior was measured as increased immobility time in the forced swim test. In both models, the onset of depression was similar between WT and T cell deficient mice, but depression was drastically prolonged in T cell deficient mice. This was associated with a prolonged upregulation of indoleamine 2,3-dioxygenase (Ido1) in the brain. Reconstitution of Rag-KO mice with T cells normalized duration of depression-like behavior and expression of brain Ido1. T cells migrated to the meninges during the resolution. The expression of Ido1 inducing cytokines such as IFNg, TNF and IL1b was T cell independent. In contrast, T cells were required for induction of IL-10 in the brain. Inhibition of brain IL-10-signaling prolonged depression-like behavior. However, the T cells were not the source of IL-10. In conclusion, T cells prevent chronicity of depression via an IL-10-dependent pathway.