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. 2002 Feb;46(2):533-44. doi: 10.1002/art.10172.


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.

MeSH terms

  • Animals
  • Antigens, Differentiation / analysis
  • Antigens, Differentiation / genetics*
  • Arthritis, Experimental / immunology*
  • Arthritis, Experimental / pathology
  • Autoantibodies / blood
  • Autoimmunity / immunology
  • CD40 Ligand / analysis
  • CD40 Ligand / biosynthesis*
  • Cell Division / immunology
  • Female
  • Flow Cytometry
  • Gene Expression / immunology
  • Human T-lymphotropic virus 1 / genetics
  • Immunoglobulin G / blood
  • Interleukin-1 / genetics*
  • Interleukin-6 / biosynthesis
  • Lymph Nodes / cytology
  • Lymphocyte Activation / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Knockout
  • T-Lymphocytes / chemistry
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Tarsus, Animal / pathology
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Antigens, Differentiation
  • Autoantibodies
  • Immunoglobulin G
  • Interleukin-1
  • Interleukin-6
  • OX40Ig
  • Tumor Necrosis Factor-alpha
  • CD40 Ligand