Our aims are to understand basic CNS immunobiology, and use that knowledge to better control desirable and unwanted immune activity.
Basic immunobiology. In the cell-mediated immune response, T cells recognize antigen plus normal cell surface proteins, the MHC proteins. In normal brain, T cells and strong MHC expression are rare, but under regulatory control. Our basic research interests include control of MHC expression and T cell traffic.
Immuno/neuro-pharmacology. An exciting new direction is to define how the local neurochemical environment affects immune regulation within the brain. This work helps us understand the characteristic localization of different neurologic disorders. It implies that therapeutic immune modulation may require different drug regimens for different sites.
Implications for harmful responses. The immune/inflammatory network is implicated in an increasing number of neurologic disorders, including MS, AD, ALS, PD, stroke, and trauma. Understanding the role of local neurochemicals can suggest new ways of reducing unwanted responses.
Implications for micro-tumor therapy. Microscopic tumor cannot be imaged or attacked by conventional means, yet is an appropriate target for immunotherapy. T cells are adapted to move through normal tissue, and selectively attack abnormal targets. Our work helps exploit this potential.
Methods include: Stereotactic injection of marked tumor cells; cytokines; T cells; neurochemicals (such as SP), agonists, and antagonists. Immunocytochemistry and histochemistry to reveal tumor, responding cells, and MHC expression in frozen sections. Computer-assisted image analysis and simple reconstructions to measure tumor, immune changes, tumor-leukocyte interactions, and their distributions in the brain. Rat models for brain tumor and autoimmunity (EAE).
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