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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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AIDS and Related Research Study Section 3 (ARRC)
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Aaron Diamond AIDS Research Center
New York
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Paxton, W A; Martin, S R; Tse, D et al. (1996) Relative resistance to HIV-1 infection of CD4 lymphocytes from persons who remain uninfected despite multiple high-risk sexual exposure. Nat Med 2:412-7
Gauduin, M C; Allaway, G P; Maddon, P J et al. (1996) Effective ex vivo neutralization of human immunodeficiency virus type 1 in plasma by recombinant immunoglobulin molecules. J Virol 70:2586-92
Telford 3rd, S R; Dawson, J E; Katavolos, P et al. (1996) Perpetuation of the agent of human granulocytic ehrlichiosis in a deer tick-rodent cycle. Proc Natl Acad Sci U S A 93:6209-14
Andrews, C A; Koup, R A (1996) The immunopathology of HIV infection. J Antimicrob Chemother 37 Suppl B:13-25
Koup, R A; Safrit, J T; Weir, R et al. (1996) Defining antibody protection against HIV-1 transmission in Hu-PBL-SCID mice. Semin Immunol 8:263-8
Gauduin, M C; Safrit, J T; Weir, R et al. (1995) Pre- and postexposure protection against human immunodeficiency virus type 1 infection mediated by a monoclonal antibody. J Infect Dis 171:1203-9
Hammond, S A; Johnson, R P; Kalams, S A et al. (1995) An epitope-selective, transporter associated with antigen presentation (TAP)-1/2-independent pathway and a more general TAP-1/2-dependent antigen-processing pathway allow recognition of the HIV-1 envelope glycoprotein by CD8+ CTL. J Immunol 154:6140-56
Safrit, J T; Koup, R A (1995) The immunology of primary HIV infection: which immune responses control HIV replication? Curr Opin Immunol 7:456-61
Kolbert, C P; Podzorski, D S; Mathiesen, D A et al. (1995) Two geographically distinct isolates of Borrelia burgdorferi from the United States share a common unique ancestor. Res Microbiol 146:415-24
Moore, J P; Cao, Y; Ho, D D et al. (1994) Development of the anti-gp120 antibody response during seroconversion to human immunodeficiency virus type 1. J Virol 68:5142-55

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