Skip to main content
SpringerLink
Log in

A gene therapy approach to treatment of autoimmune disease

  • Published:
Immunologic Research Aims and scope Submit manuscript

Abstract

New insights into the underlying mechanisms for the development of autoimmune diseases in humans and various animal models continue to increase with our understanding of factors that drive polarization of T helper (Th) responses and tolerance. This information has led to the development of new treatment strategies, including oral tolerance clinical trials and the use of altered peptide ligands in animal models. These approaches have shown some promise and provided additional insight into the disease processes. The use of gene therapy in many disease states continues to increase. We are starting to see the application of gene therapy in chronic diseases in humans. Gene therapy has been used in several animal models of autoimmune disease with promising preliminary results. In this article, an overview will be provided for the use of gene therapy in autoimmune disease.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Liblau RS, Singer SM, McDevitt HO. Th1 and Th2 CD4+ T cells in the pathogenesis of organ-specific autoimmune diseases [see comments]. Immunol Today 1995; 16, 1:34–38.

    Article  PubMed  CAS  Google Scholar 

  2. Baron JL, Madri JA, Ruddle NH, Hashim G. Janeway Jr., CA. Surface expression of alpha 4 integrin by CD4 T cells is required for their entry into brain parenchyma. J Exp Med 1993;177, 1:57–68.

    Article  PubMed  CAS  Google Scholar 

  3. van der Veen RC, Stohlman SA. Encephalitogenic Th1 cells are inhibited by Th2 cells with related peptide specificity: relative roles of interleukin (IL)-4 and IL-10. J Neuroimmunol 1993;48, 2:213–220.

    Article  PubMed  Google Scholar 

  4. Kakimoto K, Katsuki M, Hirofuji T, Iwata H, Koga T. Isolation of T cell line capable of protecting mice against collagen-induced arthritis. J Immunol 1988;140, 1:78–83.

    PubMed  CAS  Google Scholar 

  5. Swain SL. Generation and in vivo persistence of polarized Th1 and Th2 memory cells. Immunity 1994;1, 7:543–552.

    Article  PubMed  CAS  Google Scholar 

  6. Bradley LM, Yoshimoto K, Swain SL. The cytokines IL-4, IFN-gamma, and IL-12 regulate the development of subsets of memory effector helper T cells in vitro. J Immunol 1995; 155, 4:1713–1724.

    PubMed  CAS  Google Scholar 

  7. Secrist H, Chelen CJ, Wen Y, Marshall JD, Umetsu DT. Allergen immunotherapy decreases interleukin 4 production in CD4+ T cells from allergic individuals. J Exp Med 1993;178, 6:2123–2130.

    Article  PubMed  CAS  Google Scholar 

  8. Creticos PS, Marsh DG, Proud D, Kagey-Sobotka A, Adkinson Jr., NF, Friedhoff L, et al. Responses to ragweed-pollen nasal challenge before and after immunotherapy. J Allergy Clin Immunol 1989;84, 2:197–205.

    Article  PubMed  CAS  Google Scholar 

  9. Keating MU, Kagey-Sobotka A, Hamilton RG, Yunginger JW. Clinical and immunologic follow-up of patients who stop venom immunotherapy. J Allergy Clin Immunol 1991;88, 3 Pt 1:339–348.

    Article  PubMed  CAS  Google Scholar 

  10. McHugh SM, Deighton J, Stewart AG, Lachmann PJ, Ewan PW. Bee venom immunotherapy induces a shift in cytokine responses from a TH-2 to a TH-1 dominant pattern: comparison of rush and conventional immunotherapy. Clin Exp Allergy 1995;25, 9:828–838.

    Article  PubMed  CAS  Google Scholar 

  11. Varney VA, Hamid QA, Gaga M, Ying S, Jacobson M, Frew AJ, Kay AB, Durham SR. Influence of grass pollen immunotherapy on cellular infiltration and cytokine mRNA expression during allergen-induced late-phase cutaneous responses. J Clin Invest 1993;92, 2:644–651.

    PubMed  CAS  Google Scholar 

  12. Seder RA, Paul WE. Acquisition of lymphokineproducing phenotype by CD4+ T cells. Annu Rev Immunol 1994;12:635–673.

    Article  PubMed  CAS  Google Scholar 

  13. Khoury SJ, Hancock WW, Weiner HL. Oral tolerance to myelin basic protein and natural recovery from experimental autoimmune encephalomyelitis are associated with downregulation of inflammatory cytokines and differential upregulation of transforming growth factor beta, interleukin 4, and pro-staglandin E expression in the brain. J Exp Med 1992;176, 5:1355–1364.

    Article  PubMed  CAS  Google Scholar 

  14. Kennedy MK, Torrance DS, Picha KS, Mohler KM. Analysis of cytokine mRNA expression in the central nervous system of mice with experimental autoimmune encephalomyelitis reveals that IL10 mRNA expression correlates with recovery. J Immunol 1992; 149, 7:2496–2505.

    PubMed  CAS  Google Scholar 

  15. Weiner HL. Oral tolerance: immune mechanisms and treatment of autoimmune diseases. Immunol Today 1997;18, 7:335–343.

    Article  PubMed  CAS  Google Scholar 

  16. Windhagen A, Scholz C, Hollsberg P, Fukaura H, Sette A, Hafler DA. Modulation of cytokine patterns of human autoreactive T cell clones by a single amino acid substitution of their peptide ligand. Immunity 1995;2, 4:373–380.

    Article  PubMed  CAS  Google Scholar 

  17. Pfeiffer C, Stein J, Southwood S, Ketelaar H, Sette A, Bottomly K. Altered peptide ligands can control CD4 T lymphocyte differentiation in vivo. J Exp Med 1995; 181, 4:1569–1574.

    Article  PubMed  CAS  Google Scholar 

  18. Brocke S, Gijbels K, Allegretta M, Ferber I, Piercy C, Blankenstein T, et al. Treatment of experimental encephalomyelitis with a peptide analogue of myelin basic protein. Nature 1996;379, 6563: 343–346.

    Article  PubMed  CAS  Google Scholar 

  19. Trentham DE, Dynesius-Trentham RA, Orav EJ, Combitchi D, Lorenzo C, Sewell KL, et al. Effects of oral administration of type II collagen on rheumatoid arthritis [see comments]. Science 1993; 261, 5129:1727–1730.

    Article  PubMed  CAS  Google Scholar 

  20. Bonini C, Ferrari G, Verzeletti S, Servida P, Zappone E, Ruggieri L, et al. HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia [see comments]. Science 1997; 276, 5319:1719–1724.

    Article  PubMed  CAS  Google Scholar 

  21. Kohn DB. Gene therapy for hematopoietic and immune disorders. Bone Marrow Transplant 1996;18 Suppl 3:S55-S58.

    PubMed  Google Scholar 

  22. Evans CH, Robbins PD, Ghivizzani SC, Herndon JH., Kang R, Bahnson AB, et al. Clinical trial to assess the safety, feasibility, and efficacy of transferring a potentially anti-arthritic cytokine gene to human joints with rheumatoid arthritis. Hum Gene Ther 1996;7, 10:1261–1280.

    Article  PubMed  CAS  Google Scholar 

  23. Anderson WF, McGarrity GJ, Moen RC. Report to the NIH Recombinant DNA Advisory Committee on murine replicationcompetent retrovirus (RCR) assays (February 17, 1993). Hum Gene Ther 1993;4, 3:311–321.

    PubMed  CAS  Google Scholar 

  24. Qin L, Chavin KD, Ding Y, Tahara H, Favaro JP, Woodward JE, et al. Retrovirus-mediated transfer of viral IL-10 gene prolongs murine cardiac allograft survival. J Immunol 1996;156, 6:2316–2323.

    PubMed  CAS  Google Scholar 

  25. Kasahara N, Dozy AM, Kan YW. Tissue-specific targeting of retro-viral vectors through ligandreceptor interactions [see comments]. Science 1994;266, 5189: 1373–1376.

    Article  PubMed  CAS  Google Scholar 

  26. Crystal RG, Mastrangeli A, Sanders A, Cooke J, King T, Gilbert F, et al. Evaluation of repeat administration of a replication deficient, recombinant adenovirus containing the normal cystic fibrosis transmembrane conductance regulator cDNA to the airways of individuals with cystic fibrosis. Hum Gene Ther 1995;6, 5:667–703.

    PubMed  CAS  Google Scholar 

  27. Bellon G, Michel-Calemard L, Thouvenot D, Jagneaux V, Poitevin F, Malcus, C, et al. Aerosol administration of a recombinant adenovirus expressing CFTR to cystic fibrosis patients: a phase I clinical trial. Hum Gene Ther 1997;8, 1:15–25.

    PubMed  CAS  Google Scholar 

  28. Nita I, Ghivizzani SC, Galea-Lauri J, Bandara G, Georgescu HI, Robbins PD, Evans CH. Direct gene delivery to synovium. An evaluation of potential vectors in vitro and in vivo. Arthritis Rheum 1996;39, 5:820–828.

    Article  PubMed  CAS  Google Scholar 

  29. Clark KR, Sferra TJ, Johnson PR. Recombinant adeno-associated viral vectors mediate longterm transgene expression in muscle. Hum Gene Ther 1997;8, 6: 659–669.

    PubMed  CAS  Google Scholar 

  30. Qing K, Bachelot T, Mukherjee P, Wang XS, Peng L, Yoder MC, Leboulch P, Srivastava A. Adenoassociated virus type 2-mediated transfer of ecotropic retrovirus receptor cDNA allows ecotropic retroviral transduction of established and primary human cells. J Virol 1997;71, 7:5663–5667.

    PubMed  CAS  Google Scholar 

  31. Ponnazhagan S, Erikson D, Kearns WG, Zhou SZ, Nahreini P, Wang XS, Srivastava A. Lack of site-specific integration of the recombinant adeno-associated virus 2 genomes in human cells. Hum Gene Ther 1997;8, 3:275–284.

    Article  PubMed  CAS  Google Scholar 

  32. Bongioanni MR, Durelli L, Ferrero B, Imperiale D, Oggero A, Verdun E, et al. Systemic highdose recombinant-alpha-2a-interferon therapy modulates lymphokine production in multiple sclerosis. J Neurol Sci 1996; 143, 1-2:91–99.

    Article  PubMed  CAS  Google Scholar 

  33. Elliott MJ, Maini RN, Feldmann M, Long-Fox A, Charles P, Katsikis P, et al. Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factor alpha. Arthritis Rheum 1993;36, 12:1681–1690.

    Article  PubMed  CAS  Google Scholar 

  34. Elliott MJ, Maini RN, Feldmann M, Kalden JR, Antoni C, Smolen JS, et al. Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis. Lancet 1994;344, 8930:1105–1110.

    Article  PubMed  CAS  Google Scholar 

  35. Moreland LW, Baumgartner SW, Schiff MH, Tindall EA, Fleischmann RM, Weaver AL, et al. Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein [see comments]. N Engl J Med 1997;337, 3:141–147.

    Article  PubMed  CAS  Google Scholar 

  36. Linington C, Engelhardt B, Kapocs G, Lassman H. Induction of persistently demyelinated lesions in the rat following the repeated adoptive transfer of encephalitogenic T cells and demyelinating antibody. J Neuroimmunol 1992;40, 2-3:219–224.

    Article  PubMed  CAS  Google Scholar 

  37. Sobel RA, Kuchroo VK. The immunopathology of acute experimental allergic encephalomyelitis induced with myelin proteolipid protein. T cell receptors in inflammatory lesions. J Immunol 1992; 149, 4:1444–1451.

    PubMed  CAS  Google Scholar 

  38. McRae BL, Kennedy MK, Tan LJ, Dal Canto MC, Picha KS, Miller SD. Induction of active and adoptive relapsing experimental autoimmune encephalomyelitis (EAE) using an encephalitogenic epitope of proteolipid protein. J Neuroimmunol 1992;38, 3:229–240.

    Article  PubMed  CAS  Google Scholar 

  39. Shaw MK, Lorens JB, Dhawan A, Dal Canto R., Tse HY, Tran AB, et al. Local delivery of interleukin 4 by retrovirus-transduced T lymphocytes ameliorates experimental autoimmune encephalomyelitis. J Exp Med 1997;185, 9:1711–1714.

    Article  PubMed  CAS  Google Scholar 

  40. Mathisen PM, Yu M, Johnson JM, Drazba JA, Tuohy VK. Treatment of experimental autoimmune encephalomyelitis with genetically modified memory T cells. J Exp Med 1997;186, 1:159–164.

    Article  PubMed  CAS  Google Scholar 

  41. Trentham DE, Townes AS, Kang AH. Autoimmunity to typeII collagen an experimental model of arthritis. J Exp Med 1977;146, 3:857–868.

    Article  PubMed  CAS  Google Scholar 

  42. Williams RO, Mason LJ, Feldmann M, Maini RN. Synergy between anti-CD4 and anti-tumor necrosis factor in the amelioration of established collagen-induced arthritis. Proc Natl Acad Sci USA 1994;91, 7:2762–2766.

    Article  PubMed  CAS  Google Scholar 

  43. Holmdahl R, Klareskog L, Rubin K, Larsson E, Wigzell H. T lymphocytes in collagen II-induced arthritis in mice. Characterization of arthritogenic collagen II-specific Tcell lines and clones. Scand J Immunol 1985;22, 3:295–306.

    Article  PubMed  CAS  Google Scholar 

  44. Mori L, Iselin S, De Libero G, Lesslauer W, Attenuation of collagen-induced arthritis in 55-kDa TNF receptor type 1 (TNFR1)-IgG1-treated and TNFR1-deficient mice. J Immunol 1996; 157, 7:3178–182.

    PubMed  CAS  Google Scholar 

  45. Bessis N, Boissier MC, Ferrara P, Blankenstein T, Fradelizi D, Fournier C. Attenuation of collageninduced arthritis in mice by treatment with vector cells engineered to secrete interleukin-13. Eur J Immunol 1996;26, 10:2399–2403.

    Article  PubMed  CAS  Google Scholar 

  46. Chernajovsky Y, Adams G, Podhajcer OL, Mueller GM, Robbins PD, Feldmann M. Inhibition of transfer of collageninduced arthritis into SCID mice by ex vivo infection of spleen cells with retroviruses expressing soluble tumor necrosis factor receptor. Gene Ther 1995;2, 10:731–735.

    PubMed  CAS  Google Scholar 

  47. Chernajovsky Y, Adams G, Triantaphyllopoulos K, Ledda MF, Podhajcer OL. Pathogenic lymphoid cells engineered to express TGF beta 1 ameliorate disease in a collagen-induced arthritis model. Gene Ther 1997;4, 6:553–559.

    Article  PubMed  CAS  Google Scholar 

  48. Mueller R, Krahl T, Sarvetnick N. Pancreatic expression of interleukin-4 abrogates insulitis and a diabetes in nonobese diabetic (NOD) mice. J Exp Med 1996; 184, 3:1093–1099.

    Article  PubMed  CAS  Google Scholar 

  49. Moritani M, Yoshimoto K, Li S, Kondo M, Iwahana H, Yamaoka T, et al. Prevention of adoptively transferred diabetes in nonobese diabet with IL-10-transduced islet-specific Th1 lymphocytes. A gene the model for autoimmune diabetes. J Clin Invest 1996;98, 8:1851–1859.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department Medicine/Division Rheumatology and Immunology, Stanford University, 300 Pasteur Dr., Rm S021, 94305-5111, Stanford, CA

    Christine M. Seroogy & C. Garrison Fathman

Authors
  1. Christine M. Seroogy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Garrison Fathman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christine M. Seroogy.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Seroogy, C.M., Fathman, C.G. A gene therapy approach to treatment of autoimmune disease. Immunol Res 18, 15–26 (1998). https://doi.org/10.1007/BF02786510

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02786510

Key Words

Search

Navigation