Suppression of murine thyroiditis via blockade of the CD40-CD40L interaction

Immunology. 1997 Mar;90(3):421-6. doi: 10.1111/j.1365-2567.1997.00421.x.


The CD40 ligand (gp39) is transiently expressed on activated CD4+ T cells and mediates cognate helper function by interacting with CD40 on B cells. Increasing evidence suggests, however, critical involvement of gp39 not only in antibody-mediated responses but also in the development of effector T cells. Here, we have investigated the effect of in vivo gp39 blockade on the induction of murine experimental autoimmune thyroiditis (EAT), a T-cell-mediated disease. Over a 5-week period, EAT was induced in SJL mice with thyroglobulin (Tg) and adjuvant. Concomitantly, mice received intraperitoneal (i.p.) injections of MR1, a gp39-specific hamster monoclonal antibody (mAb), at 4-day intervals. Control mice were challenged with Tg but received equivalent doses of hamster immunoglobulin (HIg). It was observed that the control mice developed severe thyroiditis whereas the MR1-treated mice exhibited very low levels of infiltration that were mostly focal in nature. Blockade of gp39 was effective since the Tg-specific IgG titres were low or undetectable in all MR1-treated animals compared with the controls. In addition, upon restimulation with Tg in vitro, lymph node cells (LNC) from Tg-primed, MR1-treated mice proliferated less strongly and secreted significantly lower amounts of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) than LNC from untreated or HIg-treated controls. These results strongly suggest that in vivo blockade of gp39 suppresses EAT by inhibiting the priming of inflammatory Tg-specific T-helper type 1 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • CD40 Antigens / immunology*
  • CD40 Ligand
  • Female
  • Immunization, Passive
  • Lymphocyte Activation
  • Membrane Glycoproteins / immunology*
  • Mice
  • Mice, Inbred Strains
  • Th1 Cells / immunology
  • Thyroglobulin / immunology
  • Thyroiditis, Autoimmune / immunology*
  • Thyroiditis, Autoimmune / prevention & control


  • Antibodies, Monoclonal
  • CD40 Antigens
  • Membrane Glycoproteins
  • CD40 Ligand
  • Thyroglobulin