An interaction between antimyelin T cells and antigen-presenting glial cells is a crucial step in the cascade of immune events that lead to the inflammatory lesions in multiple sclerosis (MS). One of the most debated and controversial issues is whether microglial cells or astrocytes are the key players in initiating the (auto)immune reactions in the central nervous system in MS. Many investigators consider microglia to be the responsible intrinsic immunoeffector cells. In this review, we speculate that in MS astrocytes may serve as primary (facultative) antigen-presenting cells due to a failure of noradrenergic suppression of class II major histocompatibility complex molecules, which is caused by a loss of beta(2)-adrenergic receptors. If this hypothesis is correct, pharmacologic suppression of the antigen-presenting capacities of astrocytes may be a potential therapy for MS.

To initiate the inflammatory cascade leading to demyelination in multiple sclerosis (MS) T cells have to recognize their specific myelin antigen, which needs to be presented in the context of major histocompatibility (MHC) class II molecules expressed on antigen presenting cells. Whether astrocytes can express MHC class II molecules in vivo is a controversial issue. We performed double labeling immunohistochemistry in postmortem samples from nine patients with MS, three patients with a cerebral infarction and six controls. Astrocytes in controls, in normal appearing white matter in MS, and at the boundary of infarctions were MHC class II negative. In contrast, a subset of astrocytes in active chronic plaques immunostained for MHC class II, indicating potential antigen presenting interactions of astrocytes in MS.

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