Adjuvanticity of ISA51 and ISA720 in the induction of immune tolerance

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Abstract Various immune suppressive therapies have been used to treat autoimmune diseases, and the risks of immune suppressants can be mitigated using strategies that promote antigen-specific tolerance. Here, we report the utility of ISA51 and ISA720, a new generation of water-in-oil adjuvants in the induction of tolerance to proteolipid protein 139-151 (PLP) using the mouse model of experimental autoimmune encephalomyelitis (EAE) for multiple sclerosis. First, emulsions of ISA51 or ISA720 containing PLP 139-151 induced robust T-cell responses comparable to the complete Freund’s adjuvant (CFA)/PLP 139-151 group. Second, CFA/PLP 139-151, but not ISA51 or ISA720 emulsions induced EAE in SJL mice. Third, while splenocytes from the CFA/PLP 139-151 group produced IFN-γ, TNF-α, and IL-6, cells from ISA 51 or ISA720 groups had predominant production of IL-5, IL-9, and IL-22, but levels of IL-17A and IL-17F were comparable. However, if any, IL-4 and IL-10 levels were high in the CFA/PLP 139-151 group. Conversely, cytokines of lymph node cultures revealed high amounts of IFN-γ, IL-9, IL-10, IL-17A, IL-17F, IL-22, TNF-α, and IL-6 in the CFA/PLP 139-151 group relative to others. Strikingly, IL-5, IL-9, IL-17A, IL-17F, and IL-22 levels were elevated in ISA720/PLP 139-151 group as compared to ISA51/PLP 139-151 group. The data suggest that T cell tolerance can be induced with self-antigens emulsified in ISA51 or ISA720 independent of cytokines produced by specific T helper subsets.