Feline leukemia viral infected cats are a unique model to study immunosuppression, acquired immunodeficiency syndrome and immune mechanism(s) involved in the initiation and progression of neoplastic growth. In this proposal we plan to take advantage of the dramatic unequivocal reductions of tumor size, changes in marrow and peripheral blood, neoplastic cell populations and clearance of viremia following treatment of virus infected and/or malignant cells with SpA therapy (ex vivo immunoadsorption or injection). We will treat additional animals to determine whether the responses are biostatistically significant. We will examine both humoral (Complement (C) and C activation products) and cell mediated immunity. We will first identify T cell subsets which are poorly defined in the cat. Monoclonal antibodies (Mabs) to kitten thymocytes have been initiated and we have established for the feline system a reverse plaque hemolytic assay for evaluating B cells and roles of T helper or suppressor on induction of Ig synthesis. We now have a Mab which identifies T-S cells. A major goal is to mimic in vitro immunosuppressive FeLV effects observed in vivo i.e. to study the effects on non infectious FeLV and its purified components on T cell functions. We have already shown that U.V. FeLV has a direct suppressive effect feline IFN production and IgG secretion in vitro. Furthermore p15E peptide homologous to retroviral envelope proteins has a dramatic suppressive effect on polyclonal B cell activation by Staphylococcus Protein A. If we can show immunomodulatory influences of retrovirus and its peptides on animal or human cells, not only will we obtain a greater understanding of the in vivo potent immunosuppressive effects of retroviruses, particularly in acquired immunodeficiency syndrome, but also the immunoregulatory role of viruses may become sources of powerful pharmacologic agents.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA040931-06
Application #
3181255
Study Section
Experimental Immunology Study Section (EI)
Project Start
1985-02-01
Project End
1992-03-31
Budget Start
1990-04-05
Budget End
1991-03-31
Support Year
6
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of South Florida
Department
Type
Schools of Medicine
DUNS #
City
Tampa
State
FL
Country
United States
Zip Code
33612
Haraguchi, Soichi; Good, Robert A; Day-Good, Noorbibi K (2008) A potent immunosuppressive retroviral peptide: cytokine patterns and signaling pathways. Immunol Res 41:46-55
Haraguchi, S; Good, R A; Cianciolo, G J et al. (1997) Immunosuppressive retroviral peptides: immunopathological implications for immunosuppressive influences of retroviral infections. J Leukoc Biol 61:654-66
Kraus, L A; Bradley, W G; Engelman, R W et al. (1996) Relationship between tumor necrosis factor alpha and feline immunodeficiency virus expressions. J Virol 70:566-9
Bradley, W G; Kraus, L A; Good, R A et al. (1995) Dehydroepiandrosterone inhibits replication of feline immunodeficiency virus in chronically infected cells. Vet Immunol Immunopathol 46:159-68
Bradley, W G; Ogata, N; Good, R A et al. (1994) Alteration of in vivo cytokine gene expression in mice infected with a molecular clone of the defective MAIDS virus. J Acquir Immune Defic Syndr 7:1-9
Bush, K; Day, N K; Kraus, L A et al. (1994) Molecular cloning of feline interleukin 12 p35 reveals the conservation of leucine-zipper motifs present in human and murine IL-12 p35. Mol Immunol 31:1373-4
James-Yarish, M; Bradley, W G; Emmanuel, P J et al. (1994) Detection of cell specific cluster determinant expression by reverse transcriptase polymerase chain reaction. J Immunol Methods 169:73-82
Ogata, N; Day, N K; Buell, R D et al. (1993) Detection of the MAIDS virus using the polymerase chain reaction. PCR Methods Appl 2:272-4
Bradley, W G; Gibbs, C; Kraus, L et al. (1993) Molecular cloning and characterization of a cDNA encoding feline interleukin-6. Proc Soc Exp Biol Med 204:301-5
Haraguchi, S; Good, R A; Cianciolo, G J et al. (1993) Transcriptional down-regulation of tumor necrosis factor-alpha gene expression by a synthetic peptide homologous to retroviral envelope protein. J Immunol 151:2733-41

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