Site-specific control of T cell traffic in the brain: T cell entry to brainstem vs. hippocampus after local injection of IFN-gamma.

Although it is known that neurotransmitters and neuropeptides can affect immune function in vitro, less is understood about how the neural environment affects immune function in the brain. Previously, we showed that regulation of parenchymal class II MHC after local injection of IFN-gamma is site-specific. In this companion study, we defined the effect of local IFN-gamma on the entry of class II-restricted T cells to the brain parenchyma. To activate endogenous T cells, adult CDF rats were immunized with a normal neural antigen (MBP). Two weeks later, the proinflammatory cytokine IFN-gamma (100 to 10,000 U/site) was injected stereotaxically into two neurochemically and anatomically distinct sites, the hippocampus (area CAI) and brainstem (nucleus of the solitary tract). Monoclonal R73 was used to detect T cells on cryostat sections. The greatest difference was seen 48 h after 300 U IFN-gamma was injected at each site, when there were several-fold more parenchymal T cells in the brainstem than in the hippocampus. Most parenchymal T cells were CD4+ /class II-restricted. Thus, parenchymal T cell entry and parenchymal class II up-regulation show the same hierarchy (brainstem >> hippocampus) after local IFN-gamma injection, although T cell entry was more sensitive to the IFN-gamma dose. We suggest that the local regulatory environment contributes to site-specific immune regulation, and discuss implications for the distribution of MS plaques and other aspects of local immune control. Further, in interpreting the many previous studies of cytokine-mediated immune changes in the CNS, the possibility of site-specific differences should be considered.