Active immunization induces toxicity of diphtheria toxin in diphtheria resistant mice--implications for neuroinflammatory models

Gerd Meyer Zu Hörste; Alla L Zozulya; Houda El-Haddad; Helmar C Lehmann; Hans-Peter Hartung; Heinz Wiendl; Bernd C Kieseier

doi:10.1016/j.jim.2010.01.012

Active immunization induces toxicity of diphtheria toxin in diphtheria resistant mice--implications for neuroinflammatory models

J Immunol Methods. 2010 Mar 31;354(1-2):80-4. doi: 10.1016/j.jim.2010.01.012. Epub 2010 Feb 4.

Authors

Gerd Meyer Zu Hörste¹, Alla L Zozulya, Houda El-Haddad, Helmar C Lehmann, Hans-Peter Hartung, Heinz Wiendl, Bernd C Kieseier

Affiliation

¹ Department of Neurology, Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, Germany. [email protected]

PMID: 20138048
DOI: 10.1016/j.jim.2010.01.012

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Diphtheria Toxin / immunology
Diphtheria Toxin / toxicity*
Encephalomyelitis, Autoimmune, Experimental / genetics
Encephalomyelitis, Autoimmune, Experimental / immunology*
Encephalomyelitis, Autoimmune, Experimental / metabolism
Female
Freund's Adjuvant / immunology
Heparin-binding EGF-like Growth Factor
Humans
Immunization / adverse effects*
Intercellular Signaling Peptides and Proteins / genetics
Intercellular Signaling Peptides and Proteins / metabolism*
Lung / drug effects
Lung / immunology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neuritis, Autoimmune, Experimental / genetics
Neuritis, Autoimmune, Experimental / immunology*
Neuritis, Autoimmune, Experimental / metabolism
Ovalbumin / immunology
Peptide Fragments / immunology
Pertussis Toxin / immunology
Time Factors
Weight Loss / drug effects

Substances

Diphtheria Toxin
HBEGF protein, human
Hbegf protein, mouse
Heparin-binding EGF-like Growth Factor
Intercellular Signaling Peptides and Proteins
OVA 323-339
Peptide Fragments
Ovalbumin
Freund's Adjuvant
Pertussis Toxin