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

• Published in: Immunology 1997-03, Vol.90 (3), p.421-426
• Main Authors: CARAYANNIOTIS, G., MASTERS, S. R., NOELLE, R. J.
• Format: Article
• Language: English
• Subjects: AIDS/HIV; 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
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/j.1365-2567.1997.00421.x

SUMMARY 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‐γ (IFN‐γ) 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.