Acute shock induced by antigen vaccination in NOD mice.
Type 1 diabetes in NOD mice can be prevented through autoantigen vaccination by shifting lymphocyte differentiation toward a T-helper 2 (Th(2)) response. However, in other models of autoimmunity, this approach may be accompanied by unexpected triggering of Th(2)-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 Th(2) setting generated by 1alpha,25(OH)(2)D(3) 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 Th(1)/Th(2) cytokine profile analysis showed that the shock phenomenon was paralleled by a Th(2) response. mRNA expression of platelet-activating factor receptor (PAF-R) was significantly higher in NOD mice (P < 0.01) and was further increased by 1alpha,25(OH)(2)D(3). 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 Th(2) immune shift can result in a lethal anaphylactic reaction.
Overbergh
Lut
L
Laboratory for Experimental Medicine and Endocrinology (LEGENDO), University Hospital Gasthuisberg, Catholic University of Leuven, Belgium.
Decallonne
Brigitte
B
Branisteanu
Dumitru D
DD
Valckx
Dirk
D
Kasran
Ahmad
A
Bouillon
Roger
R
Mathieu
Chantal
C
D000818:Animals; D001324:Autoantigens / Q000008:administration & dosage*; D002117:Calcitriol / Q000009:adverse effects; D002645:Chickens; D017931:DNA Primers; D003907:Dexamethasone / Q000627:therapeutic use; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000517:prevention & control; D004195:Disease Models, Animal; D007073:Immunoglobulin E / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D009113:Muramidase / Q000276:immunology; D010980:Platelet Membrane Glycoproteins / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics; D043562:Receptors, G-Protein-Coupled; D012769:Shock / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D014612:Vaccines
D001324:Autoantigens; D017931:DNA Primers; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014612:Vaccines; C039351:platelet activating factor receptor; D007073:Immunoglobulin E; D003907:Dexamethasone; D009113:Muramidase; D002117:Calcitriol