Skip to main content

Gene Therapy-Based Approach for Immune Tolerance Induction Using Recombinant Immunoglobulin Carriers

  • Chapter
Gene Therapy of Autoimmune Diseases

Part of the book series: Medical Intelligence Unit ((MIUN))

Conclusions

The mechanisms of tolerance induction and its breakdown are important to explore because of its involvement in the pathogenesis of many known autoimmune diseases. Tolerance to “self” is not absolute and can be overcome by the immune system after a foreign stimuli caused by pathogens, allergens or other imknown immune errors (e.g., defects in apoptosis) that affect the immune system, causing a switch from tolerance to an immune response. Therefore, autoimmune diseases may often result from an aberrant or dysfunctional immune response that can no longer discriminate between “self” and “non self” proteins. This deregulation will eventually lead to a systemic disease manifested by organ or tissue specific disorder and pathogenesis. Reversal of this breakdown by the re-introduction of tolerance is therefore an important goal.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Woods JM, Katschke KJ, Volin MV et al. IL-4 Adenoviral gene therapy reduces inflammation, proinflammation cytokines, vascularization, and bony destruction in rat adjuvant-induced arthritis. J Immunol 2001; 166:1214–1222

    PubMed  CAS  Google Scholar 

  2. Chang Y, Prud’homme GJ. Intramuscular administration of expression plasmids encoding interferon-g receptor/IgGl or IL-4/IgGl chimeric proteins protects from autoimmunity. J Gene Med 1999; 1:415–423.

    Article  PubMed  CAS  Google Scholar 

  3. Costa GL, Sandora MR, Nakajima A et al. Adoptive Immunotherapy of experimental autoimmune encephalomyelitis via T cell delivery of the IL-12p40 subunit. J Immunol 2001; 167:2379–2387.

    PubMed  CAS  Google Scholar 

  4. Takiguchi M, Murakami M, Nakagawa I et al. CTLA4-IgG gene delivery prevents autoantibody production and lupus nephritis in MRL/lpr mice. Life Sci 2000; 66:991–1001.

    Article  PubMed  CAS  Google Scholar 

  5. Quattrocchi E, Dallman MJ, Feldman M. Adenovirus-mediated gene transfer of CTLA4-Ig fusion protein in the suppression of experimental autoimmune arthritis. Arthritis Rheum 2000; 43:1688–1697.

    Article  PubMed  CAS  Google Scholar 

  6. Zambidis ET, Scott DW. Epitope-specific tolerance induction with an engineered immunoglobulin. Proc Nad Acad Sci USA 1996; 93:5019–5024.

    Article  CAS  Google Scholar 

  7. Zambidis ET, Barth RK, Scott DW. Both resting and activated B lymphocytes expressing engineered peptide-Ig molecules serve as highly efficient tolerogenic vehicles in immunocompetent adult recipients. J Immunol 1997; 158:2174–2182.

    PubMed  CAS  Google Scholar 

  8. Zambidis ET, Kurup A, Scott DW. Genetically transferred central and peripheral immune tolerance via retroviral-mediated expression of immunogenic epitopes in hematopoietic progenitors or peripheral B-lymphocytes. Mol Med 1997; 3:212–224.

    PubMed  CAS  Google Scholar 

  9. Kang Y, Melo M, Deng E et al. Induction of hyporesponsiveness to intact foreign protein via retroviral-mediated gene expression: The IgG scaffold is important for induction and maintenance of immune hyporesponsiveness. Proc Natl Acad Sci USA 1999; 96:8609–8614.

    Article  PubMed  CAS  Google Scholar 

  10. El-Amine M, Melo M, Scott DW. Gene therapy for tolerance and autoimmunity: Soon to be fulfilled promises? Clin Immunol 2001; 99:1–6.

    Article  PubMed  CAS  Google Scholar 

  11. Melo M, El-Amine M, Tonnetti L et al. Gene therapeutic approaches to induction and maintenance of tolerance. Int Rev Immunol 2001; 20:627–645.

    PubMed  CAS  Google Scholar 

  12. Scott DW, Venkataraman M, Jandinski JJ. Multiple pathways of B-cell tolerance. Immunol Rev 1979; 43:241–273.

    Article  PubMed  CAS  Google Scholar 

  13. Venkataraman M, Scott DW. Cellular events in tolerance. VII. Decrease in clonable precursors stimulatable in vitro by specific antigens or LPS. Cell Immunol 1979; 47:323–331.

    Article  PubMed  CAS  Google Scholar 

  14. Aldo-Benson M, Borel Y. The tolerant cell: direct evidence for receptor blockade. J Immunol 1974; 112:1793–1803.

    PubMed  CAS  Google Scholar 

  15. Venkataraman M, Aldo-Benson M, Borel Y et al. Persistence of antigen-binding cells with surface tolerogen: Isologous versus heterologous immunoglobulin carriers. J Immunol 1977; 119:1006–1009.

    PubMed  CAS  Google Scholar 

  16. Min B, Legge LK, Caprio JC et al. Differential control of neonatal tolerance by antigen dose versus extended exposure and adjuvant. Cell Immunol 2000; 200:45–55.

    Article  PubMed  CAS  Google Scholar 

  17. Kang J, Wither J, Hozumi N. Long-term expression of a T-cell receptor beta-chain gene in mice reconstituted with retrovirus-infected hematopoietic stem cells. Proc Natl Acad Sci USA 1990; 87:9803–9807.

    Article  PubMed  CAS  Google Scholar 

  18. El-Amine M, Hinshaw JA, Scott DW. In vivo induction of tolerance by an Ig peptide is not affected by the deletion of FcR or a mutated IgG Fc fragment. Int Immunol 2002; 14:761–766.

    Article  PubMed  CAS  Google Scholar 

  19. Ravetch JV, Bolland S. IgG Fc receptors. Ann Rev Immunol 2001; 19:275–290.

    Article  CAS  Google Scholar 

  20. El-Amine M, Melo M, Kang Y et al. Mechanisms of tolerance induction by a gene-transferred peptide-IgG fusion protein expressed in B lineage cells. J Immunol 2000; 165:5631–5636.

    PubMed  CAS  Google Scholar 

  21. Krieg AM, Yi AK, Matson S et al. CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 1995; 374:546–549.

    Article  PubMed  CAS  Google Scholar 

  22. Bluestone JA. Is CTLA-4 a master switch for peripheral T cell tolerance? J Immunol 1997; 158:1989–1993.

    PubMed  CAS  Google Scholar 

  23. Krummel MF, Allison JP. CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J Exp Med 1995; 182:459–465.

    Article  PubMed  CAS  Google Scholar 

  24. Maraskovsky E, Brasel K, Teepe M et al. Dramatic increase in the numbers of functionally mature cells in Flt3 ligand-treated mice: Multiple dendritic cell subpopulations identified. J Exp Med 1996; 184:1953–1962.

    Article  PubMed  CAS  Google Scholar 

  25. Pulendran B, Smith JL, Jenkins M et al. Prevention of pripheral tolerance by a dendritic cell growth factor: Flt3 ligand as an adjuvant. J Exp Med 1998; 188:2075–2082.

    Article  PubMed  CAS  Google Scholar 

  26. Pack CD, Cestra AE, Min B et al. Neonatal exposure to antigen primes the immune system to develop responses in various lymphoid organs and promotes bystander regulation of diverse T cell specificities. J Immunol 2001; 167:4187–95.

    PubMed  CAS  Google Scholar 

  27. Agarwal RK, Kang Y, Zambidis E et al. Retroviral gene transfer of an immunoglobulin-antigen fusion construct protects from experimental autoimmune uveitis. J Clin Invest 2000; 106:245–252.

    Article  PubMed  CAS  Google Scholar 

  28. Melo M, Qian J, El-Amine M et al. Gene transfer of Ig-fusion proteins into B cells prevents and treats autoimmune diseases. J Immunol 2002; 168:4788–4795.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Eurekah.com and Kluwer Academic / Plenum Publishers

About this chapter

Cite this chapter

El-Amine, M., Litzinger, M., Melo, M.E.F., Scott, D.W. (2005). Gene Therapy-Based Approach for Immune Tolerance Induction Using Recombinant Immunoglobulin Carriers. In: Gene Therapy of Autoimmune Diseases. Medical Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/0-387-28670-5_6

Download citation

Publish with us

Policies and ethics