The specific objectives of the proposed study include the identification of the anti-HIV factor produced by CD8+ cells. The investigator will use antibodies to known cytokines and, if necessary, a variety of protein analyses. The mechanism by which CD8+ cells suppress virus in a co-culture will also be investigated. Anti-cytokine antibodies will be used as well as antibodies to known cell surface and cell recognition molecules. These latter studies would evaluate whether direct cell contact and cell recognition are involved. Another objective of the applicant is to try to define the specific CD8+ cell subset(s) responsible for anti-viral activity. Using monoclonal antibodies to a variety of cell surface proteins, the applicant will attempt to assess, by flow cytometry, the phenotype of CD8+ clones with anti-viral activity as well as to study separated CD8+ cell sub-populations from HIV-infected individuals. If the cell subset is identified, the levels of this cell type could be easily monitored by fluorescent activated cell sorter (FACS) analysis. Another objective of the applicant is to try to determine whether the anti-viral activity is HIV-specific. The investigator proposes to assess if CD8+ cells from individuals with other viral infections show anti-HIV activity and if the anti-HIV CD8+ cells suppress replication of unrelated viruses such as herpes viruses or mouse retroviruses. If the activity is HIV-specific, the applicant will attempt to determine what viral proteins induce this response. Eventually, this information could be used to """"""""educate"""""""" CD8+ cells from non-responders or from potential donors of CD8+ cells, that is, for adoptive transfer. Finally, the investigator proposes to evaluate further whether the levels of anti-CD8+ cell activity vary in HIV-infected individuals at different clinical states and after immunization with viral proteins.
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