It is well established that human immunodeficiency virus (HIV) is the causative agent of the acquired immunodeficiency syndrome (AIDS). Despite this knowledge, the exact manner in which this retrovirus effects the loss of CD4 cells, whether through direct viral cytopathology or immune-mediated lysis, remains unknown. A better understanding of the mechanisms relevant to this process will be important in the design of vaccines and therapeutic agents in the future. The recent description of HIV infection of human peripheral blood mononuclear cell-reconstituted Scid mice (Hu-Scid) allows us an animal model system in which to address the role of cell-mediated immune lysis of CD4 cells in the pathogenesis of AIDS. The overall goal of this proposal is to further characterize the Hu-Scid animal model of HIV infection, and to use this model to evaluate the in vivo role of HIV-specific cytotoxic T lymphocytes (CTL) in reducing HIV replication or producing CD4 cell loss. In addition, the role which the cellular immune response to HIV may play in protection against initial HIV infection will be addressed. In order to accomplish these ultimate goals the following specific aims will be addressed: 1. To produce a library of HIV-specific CTL clones of known antigenic specificity, epitope recognition and MHC restriction. 2. To characterize the pattern of HIV replication and resultant CD4 cell loss which occurs in HIV-infected Hu-Scid mice. 3. To study the effects of exogenously administered HIV-specific CTL clones on HIV replication and CD4 cell loss in the HIV-infected Hu-Scid mouse model.
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