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 specific T helper cells could be accomplished by delivering the antigenic peptide to antigen presenting cells. Tetanus toxin peptide residues 830-843 was chosen for these experiments. Two mammalian expression vectors carrying the genes for human Fas ligand and a chimeric invariant chain-tetanus toxin peptide construct were designed. The T cell proliferative response to tetanus toxoid was inhibited when the antigen was presented by autologus monocytes transfected with Fas ligand. T cell mixture experiments using two syngeneic T cell lines specific either for tetanus toxoid or for pertussis toxin demonstrated that the killing effect elicited by the antigen pulsed/Fas ligand-transfected antigen presenting cells was antigen specific. Finally, we demonstrated that transient expression of antigen delivered by plasmid DNA can substitute for soluble antigen in the induction of antigen-specific T cell responses. Antigen presenting cells transfected with the vector carrying Fas ligand and the vector carrying the chimeric invariant chain-peptide antigen gene were shown to inhibit antigen specific T cell reactivity. This strategy may be useful for the induction of apoptosis in allopeptide reactive T cells driving chronic rejection.
Cancedda
C
C
Division of Immunogenetics, Department of Pathology, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
Suciu-Foca
N
N
Cortesini
R
R
Harris
P E
PE
D017209:Apoptosis / Q000276:immunology; D002478:Cells, Cultured; D017637:Clonal Deletion / Q000276:immunology*; D018920:Coculture Techniques; D015536:Down-Regulation; D006801:Humans; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D010455:Peptides / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013745:Tetanus Toxoid / Q000494:pharmacology; D014170:Transformation, Genetic; D020298:U937 Cells; D019014:fas Receptor / Q000235:genetics / Q000276:immunology
D010455:Peptides; D013745:Tetanus Toxoid; D019014:fas Receptor