An Act of Balance Between Adaptive and Maladaptive Immunity in Depression: a Role for T Lymphocytes

Historically the monoaminergic neurotransmitter system, in particular the serotonergic system, was seen as being responsible for the pathophysiology of major depressive disorder (MDD). With the advent of psychoneuroimmunology an important role of the immune system in the interface between the central nervous systems (CNS) and peripheral organ systems has emerged. In addition to the well-characterised neurobiological activities of cytokines, T cell function in the context of depression has been neglected so far. In this review we will investigate the biological roles of T cells in depression. Originally it was thought that the adaptive immune arm including T lymphocytes was excluded from the CNS. It is now clear that peripheral naïve T cells not only carry out continuous surveillance within the brain but also maintain neural plasticity. Furthermore animal studies demonstrate that regulatory T lymphocytes can provide protection against maladaptive behavioural responses associated with depression. Psychogenic stress as a major inducer of depression can lead to transient trafficking of T lymphocytes into the brain stimulating the secretion of certain neurotrophic factors and cytokines. The separate and combined mechanism of CD4 and CD8 T cell activation is likely to determine the response pattern of CNS specific neurokines and neurotrophins. Under chronic stress-induced neuroinflammatory conditions associated with depression, T cell responses may become maladaptive and can be involved in neurodegeneration. Additionally, intracellular adhesion and MHC molecule expression as well as glucocorticoid receptor expression within the brain may play a role in determining T lymphocyte functionality in depression. Taken together, T lymphocyte mechanisms, which confer susceptibility or resilience to MDD, are not yet fully understood. Further insight into the cellular and molecular mechanisms which balance the adaptive and maladaptive roles of T lymphocytes may provide a better understanding of both the neuro- degenerative and -regenerative repair functions as present within the neuroimmune network during depression. Furthermore T cells may be important players in restoration of normal behaviour and immune cell homeostasis in depression.