The overall goal of this revised application is to examine cellular anti-HIV-1 cytolytic reactivities, with particular emphasis on viral envelope specificities, in order to identify those elements which may comprise a beneficial or protective versus a pathogenic immune response. A number of different priming strategies will be used in attempts to elicit MHC class I- and class-II restricted anti-HIV-1 CTL in cultures of PBMC established from seronegative donors. A portion of these studies will focus on possible allotype restriction of anti-peptide reactivities. Cell-mediated anti-viral cytotoxicities elicited in response to HIV-1 infection will be characterized with respect to antibody-directed K-cell-mediated versus CTL activities present in patients at various stages of disease as well as during disease progression in a series of longitudinal studies over an extended time course. In addition to utilizing vaccinia/HIV-1 construct infected autologous B-cell targets, cytolytic reactivities will also be measured against a panel of highly relevant target cell populations representative of viral reservoirs including HIV-1 infected T-cells, B-cells, monocytes and macrophages. Possible destructive CTL reactivities will be assessed on non-infected antigen presenting cells (APC) which have been assessed on non-infected antigen presenting cells (APC) which have been pulsed with various HIV-1 gene products with special emphasis on CD4+ cells which can bind, process and present target determinants from native gp120. Lastly, efforts will be made to determine what role CD4+ CTL may play in controlling or contributing to disease progression.

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National Institute of Allergy and Infectious Diseases (NIAID)
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Special Emphasis Panel (ARR (V1))
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Duke University
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Demarest, J F; Jack, N; Cleghorn, F R et al. (2001) Immunologic and virologic analyses of an acutely HIV type 1-infected patient with extremely rapid disease progression. AIDS Res Hum Retroviruses 17:1333-44
Tyler, D S; Stanley, S D; Bartlett, J A et al. (1998) Lymphokine-activated killer (LAK) cell anti-HIV-1 ADCC reactivity: a potential strategy for reduction of virus-infected cellular reservoirs. J Surg Res 79:115-20
Ferrari, G; Humphrey, W; McElrath, M J et al. (1997) Clade B-based HIV-1 vaccines elicit cross-clade cytotoxic T lymphocyte reactivities in uninfected volunteers. Proc Natl Acad Sci U S A 94:1396-401
Greenberg, M L; Lacey, S F; Chen, C H et al. (1997) Noncytolytic CD8 T cell-mediated suppression of HIV replication. Springer Semin Immunopathol 18:355-69
Ferrari, G; Berend, C; Ottinger, J et al. (1997) Replication-defective canarypox (ALVAC) vectors effectively activate anti-human immunodeficiency virus-1 cytotoxic T lymphocytes present in infected patients: implications for antigen-specific immunotherapy. Blood 90:2406-16
Ferrari, G; King, K; Rathbun, K et al. (1995) IL-7 enhancement of antigen-driven activation/expansion of HIV-1-specific cytotoxic T lymphocyte precursors (CTLp). Clin Exp Immunol 101:239-48
Ahearne, P M; Morgan, R A; Sebastian, M W et al. (1995) Multiple CTL specificities against autologous HIV-1-infected BLCLs. Cell Immunol 161:34-41
Toso, J F; Chen, C H; Mohr, J R et al. (1995) Oligoclonal CD8 lymphocytes from persons with asymptomatic human immunodeficiency virus (HIV) type 1 infection inhibit HIV-1 replication. J Infect Dis 172:964-73
Ferrari, G; Place, C A; Ahearne, P M et al. (1994) Comparison of anti-HIV-1 ADCC reactivities in infected humans and chimpanzees. J Acquir Immune Defic Syndr 7:325-31
Ferrari, G; Ottinger, J; Place, C et al. (1993) The impact of HIV-1 infection on phenotypic and functional parameters of cellular immunity in chimpanzees. AIDS Res Hum Retroviruses 9:647-56

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