Characterization of the interaction between astrocytes and encephalitogenic lymphocytes during the development of experimental autoimmune encephalitomyelitis ( EAE) in mice.

The nature of pathogenic mechanisms associated with the development of multiple sclerosis ( MS) have long been debated. However, limited research was conducted to define the interplay between infiltrating lymphocytes and resident cells of the central nervous system ( CNS). Data presented in this report describe a novel role for astrocyte-mediated alterations to myelin oligodendrocyte glycoprotein ( MOG)_35-55-specific lymphocyte responses, elicited during the development of experimental autoimmune encephalitomyelitis ( EAE). In-vitro studies demonstrated that astrocytes inhibited the proliferation and interferon ( IFN)-γ, interleukin ( IL)-4, IL-17 and transforming growth factor ( TGF)-β secretion levels of MOG_35-55-specific lymphocytes, an effect that could be ameliorated by astrocyte IL-27 neutralization. However, when astrocytes were pretreated with IFN-γ, they could promote the proliferation and secretion levels of MOG_35-55-specific lymphocytes, coinciding with apparent expression of major histocompatibility complex ( MHC)-II on astrocytes themselves. Quantitative polymerase chain reaction (q PCR) demonstrated that production of IL-27 in the spinal cord was at its highest during the initial phases. Conversely, production of IFN-γ in the spinal cord was highest during the peak phase. Quantitative analysis of MHC-II expression in the spinal cord showed that there was a positive correlation between MHC-II expression and IFN-γ production. In addition, astrocyte MHC-II expression levels correlated positively with IFN-γ production in the spinal cord. These findings suggested that astrocytes might function as both inhibitors and promoters of EAE. Astrocytes prevented MOG_35-55-specific lymphocyte function by secreting IL-27 during the initial phases of EAE. Then, in the presence of higher IFN-γ levels in the spinal cord, astrocytes were converted into antigen-presenting cells. This conversion might promote the progression of pathological damage and result in a peak of EAE severity. [ABSTRACT FROM AUTHOR]