Active immunization induces toxicity of diphtheria toxin in diphtheria resistant mice--implications for neuroinflammatory models.
Cell-type specific expression of the human diphtheria toxin receptor in generally toxin resistant mice represents an innovative approach for the selective depletion of pre-defined cell populations. We demonstrate that in wildtype mice diphtheria toxin--in concentrations otherwise well tolerated--is highly toxic and lethal together with active immunization irrespective of the immunogenic peptide applied. We found increased lung cellularity as only pathological abnormality. Animal models of inflammatory diseases requiring active immunization including experimental autoimmune encephalomyelitis may thus not be applicable in diphtheria receptor transgenic mice pointing to a major limitation of this otherwise technically interesting approach.
Department of Neurology, Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, Germany. gerd.mzh@uni-duesseldorf.de
Gerd
G
Meyer Zu Hörste
Alla L
AL
Zozulya
Houda
H
El-Haddad
Helmar C
HC
Lehmann
Hans-Peter
HP
Hartung
Heinz
H
Wiendl
Bernd C
BC
Kieseier
D000818:Animals; D004167:Diphtheria Toxin / Q000276:immunology / Q000633:toxicity*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005620:Freund's Adjuvant / Q000276:immunology; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D007114:Immunization / Q000009:adverse effects*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009444:Neuritis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D037342:Pertussis Toxin / Q000276:immunology; D013997:Time Factors; D015431:Weight Loss / Q000187:drug effects
D004167:Diphtheria Toxin; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; C111390:OVA 323-339; D010446:Peptide Fragments; D010047:Ovalbumin; D005620:Freund's Adjuvant; D037342:Pertussis Toxin