It is hypothesized that different HIV-associated neurological diseases have different pathogeneses. In some diseases the immune system is expected to play a primary role, in others a secondary role, and in others no role. To identify the participation of the immune response in various HIV-associated neurological diseases we propose (1) To identify the inflammatory cells and the state of activation of these cells by studying mononuclear cells in the cerebrospinal fluid, blood and tissues using flow cytometry and immunoperoxidase staining. (2) To determine the local production of inflammatory mediators in different sites using immunological and biological assays to detect and quantitate these cell products and nucleic acid hybridization assays to quantitate the corresponding mRNA. (3) To determine the effect of HIV infection on the function of human monocyte/macrophages and their production of inflammatory mediators and the portion of the long terminal repeat controlling HIV transcription in monocytes by infecting monocytes and monocyte cell lines with HIV and HIV constructs. (4) To determine whether activated lymphocytes traffic nonspecifically to the CNS independent of the presence of antigen in the CNS using passive transfer into mice of different activated cell populations purified by sedimentation and fluorescence activated cell sorting. (5) To determine the presence and level of the HIV-specific and neural tissue-specific immune responses by assaying for the presence of specific antibody in serum and CSF.
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