title: Activation of CFTR-specific T Cells in cystic fibrosis mice following gene transfer.
abstract: Gene therapy for cystic fibrosis (CF) airway disease has emerged as a potentially successful therapy, because expression of the CF gene would be expected to restore the electrophysiological function of the airway epithelium to normalcy. Although, cellular and humoral immune responses to viral gene transfer vectors have been studied extensively, there has been no evaluation of T cell-mediated responses to the therapeutic human CF gene product. Using an adenovirus vector we demonstrated that T cells against human CF gene protein are elicited in CF gene knockout (KO), heterozygote (Het), and wild-type (wt) mice. A dominant CD8 T cell epitope found in CF gene KO, Het, and wt mice was mapped to NTYLRYITV. In CF gene KO mice we also identified (to a conserved region of the CF gene CSQFSWIMPGTIKEN), a minor T cell epitope that did not show any activity in the Het or wt mice.
authors.affiliation: Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Maria P
authors.initials: MP
authors.lastname: Limberis
authors.forename: Joanita
authors.initials: J
authors.lastname: Figueredo
authors.forename: Roberto
authors.initials: R
authors.lastname: Calcedo
authors.forename: James M
authors.initials: JM
authors.lastname: Wilson
mesh_terms: D000818:Animals; D016827:CD8 Antigens / Q000276:immunology; D003550:Cystic Fibrosis / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D006801:Humans; D008168:Lung / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D016827:CD8 Antigens; D019005:Cystic Fibrosis Transmembrane Conductance Regulator