| First Author | Saijo S | Year | 2002 |
| Journal | Arthritis Rheum | Volume | 46 |
| Issue | 2 | Pages | 533-44 |
| PubMed ID | 11840457 | Mgi Jnum | J:106193 |
| Mgi Id | MGI:3617725 | Doi | 10.1002/art.10172 |
| Citation | Saijo S, et al. (2002) Suppression of autoimmune arthritis in interleukin-1-deficient mice in which T cell activation is impaired due to low levels of CD40 ligand and OX40 expression on T cells. Arthritis Rheum 46(2):533-44 |
| abstractText | OBJECTIVE: To elucidate the roles of interleukin-1 (IL-1) in the development of 2 etiologically different rheumatoid arthritis (RA) models: the type II collagen (CII)-induced arthritis (CIA) model and the human T cell leukemia virus type I transgenic (HTLV-I Tg) mouse model. METHODS: For the CIA model, DBA/1J-background IL-1alpha-/-, IL-1beta-/-, IL-1alpha/beta-/-, and wild-type littermate mice were immunized with CII. For the HTLV-I Tg model, BALB/c IL-1beta-/- or IL-1alpha/beta-/- mice were crossed with HTLV-I Tg mice. The effects of IL-1 deficiency were assessed as follows: Development of arthritis was assessed both macroscopically and microscopically. Serum antibody titer was measured by enzyme-linked immunosorbent assay. Proliferative response of lymph node cells was assayed by measurement of (3)H-thymidine incorporation. Expression of T cell surface molecule CD40 ligand (CD40L) and OX40 was determined by multicolor flow cytometric analysis. RESULTS: The development of arthritis was markedly suppressed in IL-1alpha/beta-/- mice in both models, although the effect was less prominent in HTLV-I Tg mice. Deficiency of only IL-1alpha or only IL-1beta was also associated with disease suppression. Antibody production after immunization with CII was normal in IL-1alpha/beta-/- mice, while autoantibody production was suppressed in IL-1alpha/beta-/- HTLV-I Tg mice. In IL-1alpha/beta-/- mice, the T cell proliferative response against CII was greatly reduced in both the CIA and the HTLV-I Tg models, suggesting inefficiency of T cell activation. Furthermore, expression of CD40L and OX40 on T cells was greatly reduced in IL-1alpha/beta-/- mice. CONCLUSION: These observations suggest that T cell activation by IL-1 is important for the development of autoimmunity and arthritis in these mice. |
