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 im mune function in vitro, less is understood about how the neural environment affects immune function in the brain. Previously, we showed that regulatio n of parenchymal class II MHC after local injection of IFN-gamma is site-sp ecific. In this companion study, we defined the effect of local IFN-gamma o n the entry of class Ii-restricted T cells to the brain parenchyma. To acti vate endogenous T cells, adult CDF rats were immunized with a normal neural antigen (MBP). Two weeks later, the proinflammatory cytokine IFN-gamma (10 0 to 10,000 U/site) was injected stereotaxically into two neurochemically a nd anatomically distinct sites, the hippocampus (area CAI) and brainstem (n ucleus 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-g amma was injected at each site, when there were several-fold more parenchym al T cells in the brainstem than in the hippocampus. Most parenchymal T cel ls were CD4(+)/class II-restricted. Thus, parenchymal T cell entry and pare nchymal class II up-regulation show the same hierarchy (brainstem >> hippoc ampus) after local IFN-gamma injection, although T cell entry was more sens itive to the IFN-gamma dose. We suggest that the local regulatory environme nt contributes to site-specific immune regulation, and discuss implications for the distribution of MS plaques and other aspects of local immune contr ol. Further, in interpreting the many previous studies of cytokine-mediated immune changes in the CNS, the possibility of site-specific differences sh ould be considered. (C) 1999 Elsevier Science B.V. All rights reserved.