Neuronal control of the immune response in the CNS: implications on neuronal cell death and survival
For many years, the central nervous system (CNS) was considered as an immunologically privileged organ, 1 excluded from blood-derived immune mediators and immune cells. In fact, many molecules required for the adaptive immune responses appear to be completely absent in the CNS. Expression of major histo-compatibility complex (MHC) molecules, as a prerequisite for antigen-presentation, is low or undetectable on resident cells of the nervous tissue. Meanwhile, our view about brain immunity has substantially expanded and it is now clear that the immunoprivileged status of the CNS is conditional. In the healthy organism, immune responses in the CNS are kept to a minimum. However, immune cells do not ignore the CNS. Activated T lymphocytes are capable of passing the blood-brain barrier and to invading the nervous tissue. Especially under pathological conditions, the non-immune-responsive CNS tissue turns into an inflammatory milieu, which allows bi-directional communication between resident CNS and invaded immune cells. Induction of brain immunity holds true for a huge variety of neurological diseases. Examples are disorders as diverse as CNS infections, autoimmune disease, traumatic CNS injury 2 and neurodegenerative diseases such as Alzheimer’s disease or Parkinson’s disease. 3 All these disorders share common features of immune-system induction, upregulation of MHC molecules in the pathologically changed tissue, local production of pro-inflammatory cytokines and invasion of inflammatory cells. Therefore, under these pathological conditions antigens might be presented via MHC molecules to invading T lymphocytes.