Epicutaneous Immunization with Type II Collagen Inhibits both Onset and Progression of Chronic Collagen-Induced Arthritis

Article English OPEN
Strid, Jessica ; Tan, Lee Aun ; Strobel, Stephan ; Londei, Marco ; Callard, Robin (2007)
  • Publisher: Public Library of Science
  • Journal: PLoS ONE, volume 2, issue 4 (issn: 1932-6203, eissn: 1932-6203)
  • Related identifiers: doi: 10.1371/journal.pone.0000387, pmc: PMC1849892
  • Subject: Rheumatology/Rheumatoid Arthritis | Q | Immunology/Autoimmunity | Immunology/Immunomodulation | R | Research Article | Animals, Antibodies, Arthritis, Experimental, Cell Proliferation, Collagen Type II, Disease Progression, Interferon-gamma, Mice, Mice, Inbred DBA, Skin, T-Lymphocytes | Science | Rheumatology/Autoimmunity, Autoimmune, and Inflammatory Diseases | Medicine | Dermatology/Skin and Systemic Disease

Epicutaneous immunization is a potential non-invasive technique for antigen-specific immune-modulation. Topical application of protein antigens to barrier-disrupted skin induces potent antigen-specific immunity with a strong Th2-bias. In this study, we investigate whether the autoimmune inflammatory response of chronic collagen-induced arthritis (CCIA) in DBA/1-TCR-beta Tg mice can be modified by epicutaneous immunization. We show that epicutaneous immunization with type II collagen (CII) inhibited development and progression of CCIA and, importantly, also ameliorated ongoing disease as indicated by clinical scores of disease severity, paw swelling and joints histology. Treated mice show reduced CII-driven T cell proliferation and IFN-gamma production, as well as significantly lower levels of CII-specific IgG2a serum antibodies. In contrast, CII-driven IL-4 production and IgE antibody levels were increased consistent with skewing of the CII response from Th1 to Th2 in treated mice. IL-4 production in treated mice was inversely correlated with disease severity. Moreover, T cells from treated mice inhibited proliferation and IFN-gamma production by T cells from CCIA mice, suggesting induction of regulatory T cells that actively inhibit effector responses in arthritic mice. The levels of CD4(+)CD25(+) T cells were however not increased following epicutaneous CII treatment. Together, these results suggest that epicutaneous immunization may be used as an immune-modulating procedure to actively re-programme pathogenic Th1 responses, and could have potential as a novel specific and simple treatment for chronic autoimmune inflammatory diseases such as rheumatoid arthritis.
  • References (39)
    39 references, page 1 of 4

    1. Strid J, Hourihane J, Kimber I, Callard R, Strobel S (2204) Disruption of the stratum corneum allows potent epicutaneous immunization with protein antigens resulting in a dominant systemic Th2 response. Eur J Immunol 34: 2100-2109.

    2. Wang LF, Lin JY, Hsieh KH, Lin RH (1996) Epicutaneous exposure of protein antigen induces a predominant Th2-like response with high IgE production in mice. J Immunol 156: 4077-4082.

    3. Herrick CA, Xu L, McKenzie AN, Tigelaar RE, Bottomly K (2003) IL-13 is necessary, not simply sufficient, for epicutaneously induced Th2 responses to soluble protein antigen. J Immunol 170: 2488-2495.

    4. Glenn GM, Taylor DN, Li X, Frankel S, Montemarano A, et al. (2000) Transcutaneous immunization: a human vaccine delivery strategy using a patch. Nat Med 6: 1403-1406.

    5. Partidos CD, Beignon AS, Briand JP, Muller S (2004) Modulation of immune responses with transcutaneously deliverable adjuvants. Vaccine 22: 2385-2390.

    6. Strid J, Callard R, Strobel S (2006) Epicutaneous immunization converts subsequent and established antigen-specific Th1- to Th2-type responses. Immunology 119: 27-35.

    7. Kondo H, Ichikawa Y, Imokawa G (1998) Percutaneous sensitization with allergens through barrier-disrupted skin elicits a Th2-dominant cytokine response. Eur J Immunol 28: 769-779.

    8. Feldmann M (2001) Pathogenesis of arthritis: recent research progress. Nat Immunol 2: 771-773.

    9. Feldmann M, Brennan FM, Maini RN (1996) Rheumatoid arthritis. Cell 85: 307-310.

    10. Miossec P, van den Berg W (1997) Th1/Th2 cytokine balance in arthritis. Arthritis Rheum 40: 2105-2115.

  • Similar Research Results (1)
  • Metrics
    0
    views in OpenAIRE
    0
    views in local repository
    11
    downloads in local repository

    The information is available from the following content providers:

    From Number Of Views Number Of Downloads
    UCL Discovery - IRUS-UK 0 11
Share - Bookmark