SITE SPECIFIC REGULATION OF IMMUNE FUNCTION IN THE CNS

The proposed experiments are based on the hypothesis that distinct neuroanatomical regions of the CNS of the rat will regulate immune cells differently in vivo, depending on the local profile of neurochemicals. Specifically, two major aspects of the cell-mediated immune response which are enhanced following interferon-gamma) injection - T cell traffic and MHC expression - are proposed to be differentially regulated by local CNS environments. Here, these aspects of immune function following INFO-gamma injection in the following regions: (1) the nucleus of the solitary tract (NTS), a brainstem region with primarily inhibitory neurochemicals, (2) the hippocampus, an area containing mainly excitatory neurotransmitters, and (3) the hypothalamus, a region with an abundance of neurohormones. The regulatory environments of the hippocampus and the hypothalamus are proposed to suppress T cell traffic and/or MHC expression, while enhancement of these parameters is expected to occur in the NTS. Pharmacological antagonists against specific neurochemicals will then be used to attribute differential regulation of immune function to major neurotransmitters. Finally, lesion formation after induction of experimental allergic encephalomyelitis, an animal model of multiple sclerosis, will be examined in these neuroanatomical regions to determine if pharmacological manipulation of neurotransmitters affects inflammation. The proposed studies will add insight into the factors that regulate the immune response to antigen in the CNS.