Site-specific immune regulation in the brain: Differential modulation of major histocompatibility complex (MHC) proteins in brainstem vs. hippocampus

Although neurotransmitters and neuropeptides are known to affect immune fun ction in vitro and in non-neural tissues, little is known about how the loc al mix of neurochemicals affects immune function in the brain. Here, we stu dy local modulation of the class II major histocompatibility complex (MHC) proteins, which present antigen to T cells in a key pathway for cell-mediat ed immune activity. Two sites that are well-separated anatomically and have very different neuroregulatory environments, the brainstem and hippocampus , were compared. The class II-upregulating cytokine, gamma interferon (IFN- gamma, 0.1 to 10,000 U / site), was injected stereotaxically into the hippo campus and contralateral brainstem of adult Charles-derived Fischer rats. F our days later, monoclonal antibody staining was used to detect class II MH C proteins on cryostat. sections, followed by computer-assisted image analy sis. As compared to hippocampus, the brainstem showed enhanced class TI exp ression at lower IFN-gamma doses, and reached a higher plateau. Site-specif ic class II modulation was also seen within the layers of the hippocampus, and among other brain sites. Injection of marker protein to visualize the s pread of injected protein, plus injection of IFN-gamma into alternative sit es, suggested that preferential flow cannot explain all of the site-specifi c effects. We suggest that the local neuroregulatory environment and/or int rinsic differences among target microglia are likely to play a role. Implic ations for the distribution of pathological changes, such as multiple scler osis plaques, and for local immunotherapy are discussed. (C) 1999 Wiley-Lis s, Inc.