Abstract
Objective. To study the role of the lymphotoxin (LT) signaling pathway in the development and pathogenesis of collagen-induced arthritis (CIA), and to understand the mechanisms by which blockade of the LT pathway influences the arthritogenic response to type II collagen (CII). Methods. LTα-deficient and wild-type C57BL/6 mice were immunized with CII Male DBA/1 mice were immunized with CII and treated with LTβ receptor immunoglobulin fusion protein (LT/βR-Ig) or control Ig. Mice were monitored for the development and severity of arthritis. The effects of LT blockade on immune responses were evaluated by cytokine production and antigen-specific proliferation in vitro, the delayed-type hypersensitivity (DTH) response, and serum levels of CII-specific antibodies. Results. CIA that developed in LTα-deficient mice was more severe and prolonged than that which developed in wild-type mice. Blocking LT signaling with LTβR-Ig significantly exacerbated the disease. Exacerbation of CIA was associated with an enhanced Th1-type response, including increased type 1 cytokine production, an enhanced DTH response, and elevated production of CII-specific IgG2a antibodies. Conclusion. Blockade of the LT signaling pathway exacerbates the development and progression of CIA, probably by skewing the Th1/Th2 balance that determines the outcome of autoimmune responses.
Original language | English (US) |
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Pages (from-to) | 3202-3209 |
Number of pages | 8 |
Journal | Arthritis and rheumatism |
Volume | 52 |
Issue number | 10 |
DOIs | |
State | Published - Oct 2005 |
ASJC Scopus subject areas
- Immunology and Allergy
- Rheumatology
- Immunology
- Pharmacology (medical)