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.