CD40L is necessary for the priming of effector cells for lymphocytic and granulomatous experimental autoimmune thyroiditis

J Autoimmun. 1999 Feb;12(1):1-12. doi: 10.1006/jaut.1998.0256.


The interaction of CD40 on antigen presenting cells (APC) with CD40L on mouse thyroglobulin (MTg)-specific T cells may deliver an essential signal for the development of CD4(+) experimental autoimmune thyroiditis (EAT) effector cells and anti-MTg producing B cells. To determine the requirement for CD40-CD40L interactions in G-EAT, donor mice were injected with an anti-CD40L monoclonal antibody (mAb) on days -1, 0, and +1 relative to immunization with MTg and adjuvant. Recipients of spleen cells from MTg-primed donor mice injected with anti-CD40L did not develop EAT, while spleen cells from similarly immunized hamster Ig-treated donors transferred severe G-EAT. Although the decreased EAT severity was accompanied by increased IL-4 mRNA expression by CD4(+) T cells from anti-CD40L-treated donors, the increased IL-4 was not necessary for suppression of EAT, since anti-CD40L treatment prevented EAT in IL-4-deficient mice. Addition of MTg-primed B cells during in vitro activation of spleen cells from anti-CD40L-treated donors did not induce EAT in recipients, suggesting that anti-CD40L suppresses EAT by preventing the sensitization of EAT effector cells. Addition of anti-CD40L during in vitro activation of MTg-primed spleen cells or treatment of recipients with anti-CD40L had no effect on EAT severity, indicating that CD40-CD40L interactions are not required after EAT effector cells are primed to MTg.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Autoantibodies / biosynthesis
  • Autoantibodies / immunology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • CD40 Antigens / immunology
  • CD40 Antigens / metabolism*
  • CD40 Ligand
  • Cricetinae
  • Cytokines / biosynthesis
  • Female
  • Granuloma / immunology*
  • Ligands
  • Membrane Glycoproteins / immunology*
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred CBA
  • Spleen / cytology
  • Spleen / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology
  • Thyroglobulin / biosynthesis
  • Thyroglobulin / immunology
  • Thyroiditis, Autoimmune / immunology*
  • Thyroiditis, Autoimmune / pathology
  • Thyroiditis, Autoimmune / prevention & control


  • Antibodies, Monoclonal
  • Autoantibodies
  • CD40 Antigens
  • Cytokines
  • Ligands
  • Membrane Glycoproteins
  • CD40 Ligand
  • Thyroglobulin