Gene therapy of experimental autoimmune thyroiditis by in vivo administration of plasmid DNA coding for Fas ligand.
Fas-Fas ligand (FasL) interaction is required for the maintenance of immune homeostasis and seems to be responsible for the privileged immune status of some tissues. Experimental autoimmune thyroiditis (EAT), which is characterized by autoreactive T and B cell responses and a marked lymphocytic infiltration of the thyroid, is a model of choice to study the therapeutic effects of FasL. Here, we provide evidence that direct injection of DNA expression vectors encoding FasL into the inflamed thyroid inhibited development of lymphocytic infiltration of the thyroid and induced death of infiltrating T cells. These results were paralleled by a total abrogation of anti-Tg cytotoxic T cell response in FasL-treated animals vs controls. In summary, our results show that FasL expression on thyrocytes may have a curative effect on ongoing EAT by inducing death of pathogenic autoreactive infiltrating T lymphocytes.
Batteux
F
F
Institut National de la Santé et de la Recherche Médicale, Unité 477, Université René Descartes, Paris, France.
Tourneur
L
L
Trebeden
H
H
Charreire
J
J
Chiocchia
G
G
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D004247:DNA / Q000008:administration & dosage*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D053222:Fas Ligand Protein; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000138:chemical synthesis; D008214:Lymphocytes / Q000276:immunology; D008562:Membrane Glycoproteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008808:Mice, Inbred CBA; D010957:Plasmids / Q000008:administration & dosage*; D013954:Thyroglobulin / Q000276:immunology; D013961:Thyroid Gland / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013967:Thyroiditis, Autoimmune / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
D001323:Autoantibodies; D018984:Epitopes, T-Lymphocyte; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019014:fas Receptor; D004247:DNA; D013954:Thyroglobulin