title: Adjuvant effect of diphtheria toxin after mucosal administration in both wild type and diphtheria toxin receptor engineered mouse strains.
abstract: The finding that murine and simian cells have differential susceptibility to diphtheria toxin (DTx) led to the development of genetically engineered mouse strains that express the simian or human diphtheria toxin receptor (DTR) under the control of various mouse gene promoters. Injection of DTx into DTR engineered mice allows for rapid and transient depletion of various cell populations. There are several advantages to this approach over global knockout mice, including normal mouse development and temporal control over when cell depletion occurs. As a result, many DTR engineered mouse strains have been developed, resulting in significant insights into the cell biology of various disease states. We used Foxp3(DTR) mice to attempt local depletion of Foxp3+ cells in the lung in a model of tolerance breakdown. Intratracheal administration of DTx resulted in robust depletion of lung Foxp3+ cells. However, DTx administration was accompanied by significant local inflammation, even in control C57Bl/6 mice. These data suggest that DTx administration to non-transgenic mice is not always an immunologically inert event, and proper controls must be used to assess various DTx-mediated depletion regimens.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Rochester Medical Center, 601 Elmwood Ave., Box 692, Rochester, NY 14610, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Chapman
authors.forename: Steve N
authors.initials: SN
authors.lastname: Georas
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000818:Animals; D002478:Cells, Cultured; D004167:Diphtheria Toxin / Q000008:administration & dosage* / Q000009:adverse effects; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005818:Genetic Engineering; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D006967:Hypersensitivity / Q000150:complications / Q000276:immunology / Q000628:therapy*; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007442:Intubation, Intratracheal; D008212:Lymphocyte Depletion; D008251:Macaca; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D019076:Transgenes / Q000235:genetics
chemical_list: D000276:Adjuvants, Immunologic; D004167:Diphtheria Toxin; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins
keywords: Diphtheria toxin; Lung; Regulatory T cells; Tolerance