Dexamethasone selectively retains tolerogenic macrophages in the spleen (147.19)

Abstract

Abstract We previously showed that the immunosuppressant dexamethasone (DEX), when used as a “tolerogenic adjuvant” during antigenic immunization, preferentially expands Ag-specific CD4+CD25+Foxp3+ regulatory T cells (Treg) and forcefully steers the immunization toward Ag-specific tolerance. However, the mechanisms underlying the tolerogenic efficacy of DEX remain undetermined. In this study, we show that while dose-dependently depleting dendritic cells in the spleen and lymph nodes, DEX selectively retains and modifies in the spleen a macrophage subset expressing low levels of CD11c (designated “DEX-MΦs”). DEX-MΦs constitutively express CD86 and, yet, down-regulate MHC II. Upon recall-Ag stimulation, DEX-MΦs upregulate IL-10, a classic marker for tolerogenic APCs. When presenting recall Ag in vivo, DEX-MΦs do not elicit responses of effector T cells, but rather stimulate the expansion of Ag-specific Treg. Thus, we suggest that DEX may exert its adjuvant efficacy partly by selectively retaining tolerogenic DEX-MΦs and using them as the alternate APCs.