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

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.