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

J Clin Invest. 2000 Jul;106(2):245-52. doi: 10.1172/JCI9168.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autoimmune Diseases / therapy*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / transplantation
  • Epitopes / genetics
  • Epitopes / immunology
  • Epitopes / therapeutic use
  • Eye Proteins*
  • Female
  • Genetic Therapy / methods*
  • Humans
  • Immune Tolerance
  • Immunoglobulin G / genetics
  • Immunoglobulin G / immunology
  • Immunoglobulin G / therapeutic use
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Heavy Chains / immunology
  • Immunoglobulin Heavy Chains / therapeutic use
  • Lymphocyte Transfusion
  • Mice
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology
  • Peptide Fragments / therapeutic use
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / therapeutic use
  • Retinol-Binding Proteins / genetics
  • Retinol-Binding Proteins / immunology
  • Retinol-Binding Proteins / therapeutic use*
  • Uveitis / therapy*


  • Epitopes
  • Eye Proteins
  • Immunoglobulin G
  • Immunoglobulin Heavy Chains
  • Peptide Fragments
  • Recombinant Fusion Proteins
  • Retinol-Binding Proteins
  • interstitial retinol-binding protein