The astrocyte is now recognized as a facultative immunocompetent antigen-presenting cell that can initiate intracerebral immune responses. However, despite the presence of activated T lymphocytes and their associated lymphokines within the central nervous system, there is a paucity in the expression of the major histocompatibility (MHC) antigens on normal neural tissue. These membrane-localized glycoproteins are required for the process of antigen presentation and, therefore, for the initiation of immune responses. To date, little is understood regarding the nature of inhibitory mechanisms that might be responsible for maintaining the brain as an immunoprivileged site. In this study we found that norepinephrine, a major brain transmitter, significantly inhibited y interferon-induced MHC class II antigen expression on astrocytes derived from neonatal Lewis rats. We show that this inhibition can be attenuated by the addition of a 3-adrenergic antagonist, propranolol, but not by the addition of a Pl-selective antagonist, atenolol, or by an a-adrenergic antagonist, phentolamine. Furthermore, it was found that a similar inhibition could be achieved by the addition of either dibutyrylcAMP or dipyridimole, a phosphodiesterase inhibitor. Therefore, it seems that norepinephrine-mediated inhibition of MHC class II antigen expression on astrocytes works through (32-adrenergic signal transduction pathways. Taken together, these in vitro results suggest that the brain contains inhibitory factors that may play a pivotal role in the regulation of intracerebral immune responses by modulating the expression of MHC antigens on astrocytes. The brain has been considered an immunologically privileged site (1). New studies, however, now demonstrate that the brain is in fact facultatively immunocompetent. Evidence supporting the framework of an immunocompetent brain includes the fact that activated T lymphocytes can enter and routinely survey the nervous system as well as release their associated lymphokines (2). Further, it has been shown that there is an increase in central nervous system (CNS) T-cell trafficking and in the sensitivity of T cells to myelin basic protein prior to the inception of the clinical manifestations of experimental allergic encephalomyelitis, a CNS autoimmune disorder involving demyelination (3). In multiple sclerosis, a putative autoimmune disease also involving central demyelination, intracerebral IgG synthesis has been demonstrated (4). Lastly, and perhaps most important, the brain astrocyte has now been shown to function as a facultative intracerebral antigen-presenting cell (APC), suggesting that the brain may have its own immune circuitry.For a cell to be considered an APC, it must be able to internalize, process, express, and present foreign (or self as in the case of autoimmune states) antigen to T lymphocytes as well as elaborate the T-cell growth factor interleukin 1 (5). Further, to elicit an optimal immune response, antigen must be presented to T cells (T4+ helpers) in the context of the ...
