CTL LYSIS OF HIV-INFECTED CD4 T CELLS AND MACROPHAGES

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DESCRIPTION (from abstract): Virus-specific CTL are likely to play a crucial role in host defense. Most studies of the HIV-specific response have relied on recombinant HIV-vaccinia-infected or peptide-loaded targets to monitor anti-HIV activity in vitro. In these artificial systems, HIV proteins are expressed in excess, which does not reflect their limiting concentrations in HIV-infected primary cells. Moreover, emerging data suggest that the HIV nef protein decreases the expression of the epitope-presenting molecule, HLA class I. Although macrophages are an important reservoir of HIV infection at all stages of disease, very little is known about their susceptibility to CTL recognition and lysis. In one of the aims, reproducible and feasible methods to measure CTL lysis of primary T cells and MDM infected with laboratory-adapted and clinical strains of HIV will be developed. The methods that have already been developed will be optimized to obtain uniform infection of primary cells for use as targets in CTL assays. These methods will be used to evaluate whether CTL clones and lines with different specificities and phenotypes differ in their lysis of primary targets. In the third aim, it will be determined if nef and TH2 cytokine-induced down-modulation of class I surface expression on primary T cells and MDM make them relatively resistant to CTL lysis.