Purchase this article with an account.
W. Li, A. Meyer, B. Huber; Modulation of IRBP Peptide-Specific T Cell by Gene Transfer . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4593.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: Autoimmune uveitis (AU) is an inflammatory disorder mediated by autoreactive CD4+ T cells. Interphotoreceptor binding protein (IRBP) is one of the candidate autoantigens responsible for AU. IRBP peptide 1-20 (IRBP1-20) has been identified as a major uveitogenic epitopes in a mouse model of experimental autoimmune uveitis (EAU). This study is to investigate our hypothesis that the IRBP1-20-specific T cell response can be modulated by virus-mediated gene transfer. Methods: The IRBP1-20 coding sequence is genetically fused to the ß chain of I-Ab, the only functional class II molecule in H-2b mice, through a flexible linker. Recombinant adenovirus co-expressing B7-1, a T cell co-stimulatory molecule, and the covalent complex of IRBP1-20/I-Ab was generated and characterized. IRBP1-20-specific T cell activation was investigated both in vitro with IRBP1-20-specific T cell lines and in vivo in H-2b mice. Results: In vitro results revealed that IRBP1-20-specific T cell lines can be activated by adenovirus co-expressing IRBP1-20/I-Ab and B7-1, but not by control virus. In vivo studies indicated that adenovirus co-expressing IRBP1-20/I-Ab and B7-1 can selectively activate IRBP1-20-specific T cells, but not adenoviral antigens as specificity controls. However, the adenovirus expressing IRBP1-20/I-Ab alone failed to activate peptide-specific T cells. Conclusions: These results suggest that co-expression of IRBP1-20/I-Ab and B7-1 leads to peptide-specific T cell activation in a T cell receptor-guided fashion. This approach is potentially applicable to turn off EAU by down-regulating the peptide-specific T cell response in conjunction with inhibitory molecules, such as Fas ligand or programmed death-1 ligands.
This PDF is available to Subscribers Only