Lethal Shock Induced by Streptococcal Pyrogenic Exotoxin A in Mice Transgenic for Human Leukocyte Antigen–DQ8 and Human CD4 Receptors: Implications for Development of Vaccines and Therapeutics

Streptococcal and staphylococcal infections result in significant human morbidity and mortality. This study used a transgenic murine model expressing human major histocompatibility complex (MHC) class II and human CD4 in which, without additional toxic sensitization, human-like responses to the bact...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of infectious diseases 2002-08, Vol.186 (4), p.501-510
Main Authors: Welcher, Brent C., Carra, John H., DaSilva, Luis, Hanson, Juli, David, Chella S., Aman, M. Javad, Bavari, Sina
Format: Article
Language:English
Subjects:
Animals
Bacterial diseases
Bacterial Proteins
Biological and medical sciences
CD4 Antigens - genetics
CD4 Antigens - metabolism
Cytokines
Cytokines - blood
Disease Models, Animal
Exotoxins
Exotoxins - genetics
Exotoxins - immunology
Exotoxins - toxicity
Experimental bacterial diseases and models
HLA-DQ Antigens - genetics
HLA-DQ Antigens - metabolism
Humans
Infectious diseases
Liver - enzymology
Major Articles
Medical sciences
Membrane Proteins
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Transgenic
Molecules
Receptors, Antigen, T-Cell, alpha-beta - metabolism
Shock, Septic - etiology
Shock, Septic - immunology
Shock, Septic - mortality
Streptococcal Infections - etiology
Streptococcal Infections - prevention & control
Streptococcal Vaccines - administration & dosage
Streptococcal Vaccines - immunology
Streptococcus pyogenes - immunology
Superantigens
Superantigens - immunology
Superantigens - toxicity
T lymphocytes
T-Lymphocytes - immunology
Toxicity
Toxins
Transgenes
Transgenic animals
Vaccination
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Streptococcal and staphylococcal infections result in significant human morbidity and mortality. This study used a transgenic murine model expressing human major histocompatibility complex (MHC) class II and human CD4 in which, without additional toxic sensitization, human-like responses to the bacterial superantigen (SAg) streptococcal pyrogenic exotoxin A (SpeA) could be simulated, as determined by studying multiple biologic effects of the SAgs in vivo. Expression of human leukocyte antigen (HLA)–DQ8 rendered the mice susceptible to SpeA-induced lethal shock that was accompanied by massive cytokine production and marked elevation of serum alanine and aspartate aminotransferase levels. Of importance, this model enabled examination of the efficacy of an engineered non-SAg vaccine candidate against SpeA in the context of HLA. This report is thought to be the first of a lethal shock triggered in mice by bacterial SAgs without prior sensitization and examination of a vaccine against streptococcal SAg in the context of human MHC receptors
ISSN:0022-1899
1537-6613
DOI:10.1086/341828