The effect of aluminum adjuvants on dendritic cells
Aluminum compounds are commonly used as adjuvants in human and veterinary vaccines. The mechanism by which aluminum-containing adjuvants enhance the immune response is not well understood. The effect of aluminum-containing adjuvants on the phenotype, antigen presentation and cytokine production by mouse bone marrow-derived dendritic cells (BMDCs) was investigated. Aluminum-containing adjuvants induced expression of CD86 on BMDCs but did not increase the expression of major histocompatibility complex (MHC) class II, CD80, B7-RP or CD40 molecules. Treatment of BMDCs with aluminum-containing adjuvants increased the mRNA expression of CCR7. This chemokine receptor is important for the migration of dendritic cells (DCs) to lymph nodes. Aluminum-containing adjuvants stimulated IL-1β and IL-18 release from BMDCs via caspase-1 activation, whereas lipopolysaccharide (LPS) stimulated only IL-1β but not IL-18 secretion. BMDCs pulsed with ovalbumin (OVA) adsorbed to aluminum-containing adjuvants activated the antigen-specific T cells more effectively than BMDCs pulsed with OVA alone. Blocking IL-1β activity with a specific antibody did not affect the ability of BMDCs to present OVA to OVA-specific T cells. Aluminum/OVA-activated BMDCs primed T cells to produce IFN-γ as well as IL-4 and IL-5. In contrast, LPS/OVA only induced T cell to produce IFN-γ. Addition of neutralizing anti-IL-1β antibodies resulted in approximately a 50% decrease in IL-5 production and addition of anti-IL-18 antibodies resulted in a 50--60% decrease of both IL-4 and IL-5 production. Treatment of BMDCs with aluminum-containing adjuvants increased the mRNA expression of the Notch ligand Jagged2, a molecule known to instruct differentiation of CD4+ T cells toward TH2 effector cells. These results suggest that aluminum-containing adjuvants directly activate DCs, enhance the ability of DCs to present antigen to T cells and induce DCs to differentiate T cells predominantly toward TH2 effector cells.
HogenEsch, Purdue University.
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