Abstract: One major problem with adenovirus gene therapy has been the T-cell mediated immune response elicited by inoculation of adenovirus, which leads to rapid clearance of the virus and loss of transgene expression. In the instant invention, the immune response to a virus is prevented by pre-treatment with adenovirus, adenoassociated virus or herpes virus infected antigen-presenting cell (APC) expressing Fas ligand with induced T-cell tolerance. Administration of AdCMVLacZ after tolerance resulted in prolonged expression of LacZ in tolerized animals compared to control treated animals. In control, but not tolerized animals, there was proliferation of CD3+T-cell in the spleen in response to AdCMVLacZ treatment. Tolerance induction is also indicated by decreased production of interferon-&ggr; and IL-2 by peripheral T-cells isolated from treated animals after stimulation with the adenovirus infected APCs.

Abstract: One major problem with adenovirus gene therapy has been the T-cell mediated immune response elicited by inoculation of adenovirus, which leads to rapid clearance of the virus and loss of transgene expression. In the instant invention, the immune response to a virus is prevented by pre-treatment with adenovirus, adenoassociated virus or herpes virus infected antigen-presenting cell (APC) expressing Fas ligand with induced T-cell tolerance. Administration of AdCMVLacZ after tolerance resulted in prolonged expression of LacZ in tolerized animals compared to control treated animals. In control, but not tolerized animals, there was proliferation of CD3+ T-cell in the spleen in response to AdCMVLacZ treatment. Tolerance induction is also indicated by decreased production of interferon-&ggr; and IL-2 by peripheral T-cells isolated from treated animals after stimulation with the adenovirus infected APCs.

Abstract: The present invention provides a method of increasing adenoviral gene expression in a tissue of an animal, comprising the step of administering to said animal a pharmacologically effective dose of tumor necrosis factor binding protein. Also provided is a various method of method of reducing an inflammatory response associated with adenoviral administration in a tissue of an animal, comprising the step of administering to said animal a pharmacologically effective dose of tumor necrosis factor binding protein.

Abstract: The present invention discloses a method of producing large-scale recombinant adeno-associated virus stocks by infection of cells with at least one recombinant adenovirus vector(s). The vector(s) encode a therapeutic gene flanked by the terminal repeat ends of adeno-associated virus and the adeno-associated virus rep and cap genes. Transfection with two recombinant adenovirus vector(s) instead of two plasmids plus adenovirus results in the large scale, high titer production of recombinant adeno-associated virus with little to no contaminating adenovirus present.

Abstract: The present invention provides a method of inducing systemic tolerance to an antigen in an individual in need of such treatment, comprising the step of: administering antigen presenting cells to said individual, wherein said cells express Fas ligand and said antigen.

Abstract: The present invention provides a method of increasing adenoviral gene expression in a tissue of an animal, comprising the step of administering to said animal a pharmacologically effective dose of tumor necrosis factor binding protein. Also provided is a various method of method of reducing an inflammatory response associated with adenoviral administration in a tissue of an animal, comprising the step of administering to said animal a pharmacologically effective dose of tumor necrosis factor binding protein.

Abstract: The present invention provides a transgenic mouse containing a transgene, said transgene comprising a truncated Nur77 (.DELTA.Nur77) gene. Also provided is a double transgenic mouse, wherein said double transgenic mouse comprises the .DELTA.Nur77 transgenic mouse backcrossed with the D.sup.b /HY T cell receptor transgenic mouse.

Abstract: Disclosed is a 5' flanking sequence of the human fas gene containing a promoter region. This sequence also contains at least three transcription initiation sites, as well as consensus sequences for AP-1, GF-1, NY-Y, CP-2, EB20, and c-myb. Also disclosed are methods of altering senescence of the immune system by modifying Fas activity in cells to increase or decrease apoptosis. Fas expression and function on T cells from old (22-26-month-old) mice is also compared to young (2-month-old) mice and old CD2-fas transgenic mice. Fas expression and ligand-induced apoptosis was decreased on T cells from old mice compared to young mice. In 26-month-old CD2-fas transgenic mice, Fas and CD44 expression, Fas-induced apoptosis, T cell proliferation and cytokine production were comparable to that of the young mice.