LOCAL CONTROL OF IMMUNE ACTIVITY IN THE BRAIN

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DESCRIPTION (Applicant's Abstract): Neuropeptides can affect leukocytes in vitro and immune responses in vivo. Here the question asked is, do local neuropeptides affect immune behavior within the brain itself? The investigators study two key features of the T cell-mediated response: T-cell entry, and expression of the MHC proteins that present antigens to T cells. They examine MHC expression and T cell entry in normal rats, and at sites of brain tumor growth. The neuropeptide the investigators are studying is substance P (SP). The local site they study is the brain stem. Brain stem glioma is an important and devastating tumor, particularly in childhood. The tumor's location and growth pattern make T-cell mediated therapy of special interest. SP is abundant in the brain stem. Here they define its local immunologic effects. This work has basic and clinical interest. Hypotheses: (1) Immune regulation in the normal brain is site-specific. (2) Immune regulation is still possible, and still site-specific, in the presence of growing tumor. (3) The local neuro-regulatory environment contributes to site-specific regulation. In particular, the immune-enhancing neuropeptide, substance P (SP), can enhance IFN-g's effects. Methods: T cell entry, MHC expression, T-cell/tumor interactions are studied quantitatively, using the model developed by the investigators. Methods include stereotactic injection, antibody staining of cryostat sections, and computer-assisted image analysis. Rats are used.