RRC ID 51319
Author Zhou B, Liao Y, Guo Y, Tarner IH, Liao C, Chen S, Kermany MH, Tu H, Zhong S, Chen P.
Title Adoptive Cellular Gene Therapy for the Treatment of Experimental Autoimmune Polychondritis Ear Disease.
Journal ORL J. Otorhinolaryngol. Relat. Spec.
Abstract In the past, the clinical therapy for autoimmune diseases, such as autoimmune polychondritis ear disease, was mostly limited to nonspecific immunosuppressive agents, which could lead to variable responses. Currently, gene therapy aims at achieving higher specificity and less adverse effects. This concept utilizes the adoptive transfer of autologous T cells that have been retrovirally transduced ex vivo to express and deliver immunoregulatory gene products to sites of autoimmune inflammation. In the animal model of collagen-induced autoimmune polychondritis ear disease (CIAPED), the adoptive transfer of IL-12p40-expressing collagen type II (CII)-specific CD4+ T-cell hybridomas resulted in a significantly lower disease incidence and severity compared with untreated or vector-only-treated animals. In vivo cell detection using bioluminescent labels showed that transferred CII-reactive T-cell hybridomas accumulated in the inflamed earlobes of the mice with CIAPED. In vitro analysis demonstrated that IL-12p40-transduced T cells did not affect antigen-specific T-cell activation or systemic anti-CII Ab responses. However, IL-12p40-transduced T cells suppressed IFN-γ and augmented IL-4 production, indicating their potential to act therapeutically by interrupting Th1-mediated inflammatory responses via augmenting Th2 responses. These results indicate that the local delivery of IL-12p40 by T cells could inhibit CIAPED by suppressing autoimmune responses at the site of inflammation.
Volume 79(3)
Pages 166-177
Published 2017
DOI 10.1159/000452767
PII 000452767
PMID 28463837
MeSH Adoptive Transfer / methods* Analysis of Variance Animals Autoimmune Diseases / therapy* Biopsy, Needle Disease Models, Animal Ear Diseases / immunology Ear Diseases / pathology Ear Diseases / therapy* Female Genetic Therapy / methods* Immunohistochemistry Interleukin-12 Subunit p40 / therapeutic use* Mice Mice, Inbred DBA Polychondritis, Relapsing / pathology Polychondritis, Relapsing / therapy* Random Allocation
IF 1.012
Resource
DNA material