Suppression of the cellular adjuvanticity of lipophilic amines by a polyanion.
Modulation of delayed-type hypersensitivity reaction (DTH) in mice by synthetic adjuvants and the mode of their action were investigated. Intracutaneous injection of azobenzenearsonate coupled to phosphatidylethanolamine (A-PE) without adjuvant did not induce DTH. Administration of A-PE with the quaternary amines dimethyldioctadecylammonium bromide (DDA) or N,N-dioctadecyl-N',N'-bis(2-hydroxyethyl)propane diamine (CP-20,961) induced a strong response. Other surfactants, dextran sulfate (DXS) and dextran were not effective. In combination with 200 nmol DDA the optimal dose of antigen was 5 nmol A-PE, while at higher antigen doses DTH was diminished. Responses on combination of two adjuvants and A-PE revealed that DXS counteracted the stimulatory effects of both DDA and CP-20,961. In vitro, DDA formed insoluble complexes with 14C-A-PE and at optimal antigen concentration more than 90% of the antigen was bound to the adjuvant. The percentage of 14C-A-PE bound to 200 nmol DDA decreased with increasing doses of 14C-A-PE. Addition of DXS to the mixture of 14C-A-PE and DDA reduced the percentage of 14C-A-PE bound to DDA. Dose-response curves demonstrated a close relationship between the inhibitory effects of DXS on the DTH and the A-PE/DDA complex formation. Nonsulfated dextran affected neither the DTH nor the formation of complexes in vitro. In conclusion, cellular adjuvanticity of DDA for the lipophilic antigen A-PE is probably the result of formation of insoluble complexes with the antigen. Free A-PE suppresses the cellular response to A-PE/DDA complexes. The adjuvant DXS inhibits DTH by reducing the amount of immunogenic A-PE/DDA complexes and thus increasing the amount of free, immunosuppressive A-PE.
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D003634:DDT / Q000031:analogs & derivatives* / Q000494:pharmacology; D003959:Diamines / Q000494:pharmacology*; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007108:Immune Tolerance; D007111:Immunity, Cellular / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C
D000276:Adjuvants, Immunologic; D003959:Diamines; C000849:bis(p-chlorophenyl)acetic acid; D003634:DDT; C006270:avridine