Neuronal Modulation of the Immune Response in Nervous Tissue: Implications for Neurodegenerative and Autoimmune Diseases

Abstract

This review summarizes recent data highlighting an interconnection between the nervous and the immune system which may be relevant for developing an effective therapy for neurodegenerative or autoimmune diseases. Traditionally, neurodegenerative diseases have been considered as local nervous system processes with no conceivable pathogenic link to inflammatory or autoimmune diseases of the nervous system. However, this view does not explain the local immune response that occurs in lesions of primary neurodegenerative processes. This response is characterized by up-regulation of major histocompatibility complex (MHC) molecules and immune-like infiltrations. One example is amyotrophic lateral sclerosis, which in some cases appears to be triggered by a point mutation in the superoxide dismutase gene (Andersen et al. 1995). Lymphocytes and monocytes form prominent infiltrates and MHC molecules are induced on microglia in areas of the central nervous system (CNS) affected by degeneration (Lampson et al. 1990; Kawamata et al. 1992). Similar signs of local immune activation are detectable in other neurodegenerative processes such as Parkinson’s or Alzheimer’s disease. In the latter, CD4 and CD8 T lymphocytes infiltrate the lesioned areas and microglia cells are activated to attain antigen-presenting properties.