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Acute Shock Induced by Antigen Vaccination in NOD Mice

¹ Laboratory for Experimental Medicine and Endocrinology (LEGENDO), University Hospital Gasthuisberg, Catholic University of Leuven, Leuven, Belgium
² Clinic of Endocrinology, University Hospital "St. Spiridon," University of Medicine and Pharmacy "Gr. T. Popa," Iasi, Romania
³ Laboratory for Immunology, University Hospital Gasthuisberg, Catholic University of Leuven, Leuven, Belgium

Type 1 diabetes in NOD mice can be prevented through autoantigen vaccination by shifting lymphocyte differentiation toward a T-helper 2 (Th₂) response. However, in other models of autoimmunity, this approach may be accompanied by unexpected triggering of Th₂-dependent anaphylactic shock. To test the safety of vaccination therapy in the NOD mouse model, we evaluated the effects of immunization with a wide battery of antigens in NOD, BALB/c, and C57BL/6 mice. Surprisingly, a nondiabetogenic antigen, hen egg white lysozyme, induced severe shock exclusively in NOD mice (shock in 11 of 11 mice, lethal in 3 mice). Shock severity was further increased by a more pronounced Th₂ setting generated by 1,25(OH)₂D₃ administration (17 of 17 mice, lethal in 14 mice, P < 0.0001). Pretreatment with dexamethasone resulted in full rescue, indicating an immune-mediated mechanism. Serum IgE levels and Th₁/Th₂ cytokine profile analysis showed that the shock phenomenon was paralleled by a Th₂ response. mRNA expression of platelet-activating factor receptor (PAF-R) was significantly higher in NOD mice (P < 0.01) and was further increased by 1,25(OH)₂D₃. Pretreatment with WEB2086 (PAF-R antagonist) again protected all mice from lethal shock, indicating PAF as an anaphylaxis effector. In conclusion, in NOD mice, vaccination leading to a Th₂ immune shift can result in a lethal anaphylactic reaction.

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