May 2003
Volume 44, Issue 13
ARVO Annual Meeting Abstract  |   May 2003
Modulation of IRBP Peptide-Specific T Cell by Gene Transfer
Author Affiliations & Notes
  • W. Li
    Ophthalmology, University Miami Sch Med, Miami, FL, United States
  • A. Meyer
    Pathology, Tufts University, Boston, MA, United States
  • B. Huber
    Pathology, Tufts University, Boston, MA, United States
  • Footnotes
    Commercial Relationships  W. Li, None; A. Meyer, None; B. Huber, None.
  • Footnotes
    Support  NIH grant EY13698
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 4593. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      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)

  • Supplements

Abstract: : 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.

Keywords: uveitis-clinical/animal model • gene transfer/gene therapy • autoimmune disease 

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.