• Dexamethasone;
  • Macrophage;
  • Tolerance

We previously showed that antigen immunization in the presence of the immunosuppressant dexamethasone (a strategy we termed “suppressed immunization”) could tolerize established recall responses of T cells. However, the mechanism by which dexamethasone acts as a tolerogenic adjuvant has remained unclear. In the present study, we show that dexamethasone enriches CD11cloCD40lo macrophages in a dose-dependent manner in the spleen and peripheral lymph nodes of mice by depleting all other CD11c+CD40+ cells including dendritic cells. The enriched macrophages display a distinct MHC class II (MHC II)loCD86hi phenotype. Upon activation by antigen in vivo, CD11cloCD40lo macrophages upregulate IL-10, a classic marker for tolerogenic antigen-presenting cells, and elicit a serum IL-10 response. When presenting antigen in vivo, these cells do not elicit recall responses from memory T cells, but rather stimulate the expansion of antigen-specific regulatory T cells. Moreover, the depletion of CD11cloCD40lo macrophages during suppressed immunization diminishes the tolerogenic efficacy of the treatment. These results indicate that dexamethasone acts as a tolerogenic adjuvant partly by enriching the CD11cloCD40lo tolerogenic macrophages.