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.
For the CIA model, DBA/1J-background IL-1α−/−, IL-1β−/−, IL-1α/β−/−, and wild-type littermate mice were immunized with CII. For the HTLV-I Tg model, BALB/c IL-1β−/− or IL-1α/β−/− 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 3H-thymidine incorporation. Expression of T cell surface molecule CD40 ligand (CD40L) and OX40 was determined by multicolor flow cytometric analysis.
The development of arthritis was markedly suppressed in IL-1α/β−/− mice in both models, although the effect was less prominent in HTLV-I Tg mice. Deficiency of only IL-1α or only IL-1β was also associated with disease suppression. Antibody production after immunization with CII was normal in IL-1α/β−/− mice, while autoantibody production was suppressed in IL-1α/β−/− HTLV-I Tg mice. In IL-1α/β−/− 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-1α/β−/− mice.
These observations suggest that T cell activation by IL-1 is important for the development of autoimmunity and arthritis in these mice.