Abstract: The present invention relates to methods and compositions for inhibiting pancreatic &bgr; cell dysfunction and Fas-mediated apoptosis. The invention relates to recombinant vectors, including viral vectors, comprising nucleic acids molecules encoding inhibitors of interleukin-1&bgr; (IL-1&bgr;) and Fas-mediated apoptosis and the use of such vectors for transfer of said nucleic acid molecules into &bgr; cells. The invention encompasses genetically engineered &bgr; cells comprising nucleic acid molecules encoding inhibitors of IL-1&bgr; signal transduction. The invention further relates to methods for transplanting such genetically engineered &bgr; cells into a host recipient with a pancreatic disorder. The methods and compositions of the invention may be used to reduce Il-1&bgr; mediated &bgr; cell dysfunction and apoptosis, thereby reducing the insulitis associated with pancreatic disorders such as insulin dependent diabetes mellitus (IDDM).

Abstract: The present invention relates to tolerogenic mammalian dendritic cells (DCs) and methods for the production of the tolerogenic DCs. In addition, the present invention provides a method for enhancing tolerogenicity in a host comprising administering the tolerogenic mammalian DCs of the present invention to the host. The tolerogenic DCs of the present invention comprise an oligodeoxyribonucleotide (ODN) which has one or more NF-&kgr;B binding sites. The tolerogenic DCs of the present invention may further comprise a viral vector, and preferably an adenoviral vector, which does not affect the tolerogenicity of the tolerogenic DCs when present therein. Enhanced tolerogenicity in a host is useful for prolonging foreign graft survival and for treating inflammatory related diseases, such as autoimmune diseases.