We have determined in mice the minimum composition required for forming a vaccine adjuvant that stimulates a regulatory T (Treg) cell response to immunization, and we named the adjuvant "complete tolerogenic adjuvant." This new kind of adjuvant may let us use the well-proven "Ag with adjuvant" form of immunization for inducing Treg cell-mediated Ag-specific immunosuppression. The minimum composition consists of dexamethasone, rapamycin, and monophosphoryl lipid A at a mass ratio of 8:20:3. By dissecting the respective role of each of these components during immunization, we have further shown why immunosuppressive and immunogenic agents are both needed for forming true adjuvants for Treg cells. This finding may guide the design of additional, and potentially more potent, complete tolerogenic adjuvants with which we may form numerous novel vaccines for treating immune diseases.
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