HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Retroviral gene therapy with an immunoglobulin-antigen fusion construct protects from experimental autoimmune uveitis.

Abstract
Immunoglobulins can serve as tolerogenic carriers for antigens, and B cells can function as tolerogenic antigen-presenting cells. We used this principle to design a strategy for gene therapy of experimental autoimmune uveitis, a cell-mediated autoimmune disease model for human uveitis induced with the uveitogenic interphotoreceptor retinoid-binding protein (IRBP). A retroviral vector was constructed containing a major uveitogenic IRBP epitope in frame with mouse IgG1 heavy chain. This construct was used to transduce peripheral B cells, which were infused into syngeneic recipients. A single infusion of transduced cells, 10 days before uveitogenic challenge, protected mice from clinical disease induced with the epitope or with the native IRBP protein. Protected mice had reduced antigen-specific responses, but showed no evidence for a classic Th1/Th2 response shift or for generalized anergy. Protection was not transferable, arguing against a mechanism dependent on regulatory cells. Importantly, the treatment was protective when initiated 7 days after uveitogenic immunization or concurrently with adoptive transfer of primed uveitogenic T cells. We suggest that this form of gene therapy can induce epitope-specific protection not only in naive, but also in already primed recipients, thus providing a protocol for treatment of established autoimmunity.
AuthorsR K Agarwal, Y Kang, E Zambidis, D W Scott, C C Chan, R R Caspi
JournalThe Journal of clinical investigation (J Clin Invest) Vol. 106 Issue 2 Pg. 245-52 (Jul 2000) ISSN: 0021-9738 [Print] United States
PMID10903340 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Epitopes
  • Eye Proteins
  • Immunoglobulin G
  • Immunoglobulin Heavy Chains
  • Peptide Fragments
  • Recombinant Fusion Proteins
  • Retinol-Binding Proteins
  • interstitial retinol-binding protein
Topics
  • Animals
  • Autoimmune Diseases (therapy)
  • B-Lymphocytes (immunology, transplantation)
  • Epitopes (genetics, immunology, therapeutic use)
  • Eye Proteins
  • Female
  • Genetic Therapy (methods)
  • Humans
  • Immune Tolerance
  • Immunoglobulin G (genetics, immunology, therapeutic use)
  • Immunoglobulin Heavy Chains (genetics, immunology, therapeutic use)
  • Lymphocyte Transfusion
  • Mice
  • Peptide Fragments (genetics, immunology, therapeutic use)
  • Recombinant Fusion Proteins (immunology, therapeutic use)
  • Retinol-Binding Proteins (genetics, immunology, therapeutic use)
  • Uveitis (therapy)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: