Specific T cell deletion by transfected human monocytes expressing Fas ligand and antigen

The aim of our experiments was to determine whether deletion of antigen spe cific T helper cells could be accomplished by delivering the antigenic pept ide to antigen presenting cells. Tetanus toxin peptide residues 830-843 was chosen for these experiments. Two mammalian expression vectors carrying th e genes for human Fas ligand and a chimeric invariant chain-tetanus toxin p eptide construct were designed. The T cell proliferative response to tetanu s toroid was inhibited when the antigen was Presented by autologus monocyte s transfected with Fas ligand. T cell mixture experiments using two syngene ic T cell lines specific either for tetanus toroid or for pertussis toxin d emonstrated that the killing effect elicited by the antigen pulsed/Fas liga nd-transfected antigen presenting cells was antigen specific. Finally, we d emonstrated that transient expression of antigen delivered by plasmid DNA c an substitute for soluble antigen in the induction of antigen-specific T ce ll responses. Antigen presenting cells transfected with thr vector carrying Fas ligand and the vector carrying the chimeric invariant chain-peptide an tigen gene were shown to inhibit antigen specific T cell reactivity. This s trategy may be useful for the induction of apoptosis in allopeptide reactiv e T cells driving chronic rejection. (C) American Society for Histocompatib ility and Immunogenetics, 2000. Published by Elsevier Science Inc.