PMID- 12195377
OWN - NLM
STAT- MEDLINE
DCOM- 20020917
LR  - 20171116
IS  - 0022-1899 (Print)
IS  - 0022-1899 (Linking)
VI  - 186
IP  - 4
DP  - 2002 Aug 15
TI  - 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.
PG  - 501-10
AB  - 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.
FAU - Welcher, Brent C
AU  - Welcher BC
AD  - Department of Cell Biology and Biochemistry, US Army Medical Research Institute 
      of Infectious Diseases, Frederick, Maryland, USA. bwelche@mail.nih.gov
FAU - Carra, John H
AU  - Carra JH
FAU - DaSilva, Luis
AU  - DaSilva L
FAU - Hanson, Juli
AU  - Hanson J
FAU - David, Chella S
AU  - David CS
FAU - Aman, M Javad
AU  - Aman MJ
FAU - Bavari, Sina
AU  - Bavari S
LA  - eng
GR  - AI-14764/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20020719
PL  - United States
TA  - J Infect Dis
JT  - The Journal of infectious diseases
JID - 0413675
RN  - 0 (Bacterial Proteins)
RN  - 0 (CD4 Antigens)
RN  - 0 (Cytokines)
RN  - 0 (Exotoxins)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ8 antigen)
RN  - 0 (Membrane Proteins)
RN  - 0 (Receptors, Antigen, T-Cell, alpha-beta)
RN  - 0 (SpeA protein, Streptococcus pyogenes)
RN  - 0 (Streptococcal Vaccines)
RN  - 0 (Superantigens)
RN  - 0 (erythrogenic toxin)
SB  - IM
MH  - Animals
MH  - *Bacterial Proteins
MH  - CD4 Antigens/*genetics/metabolism
MH  - Cytokines/blood
MH  - *Disease Models, Animal
MH  - Exotoxins/genetics/immunology/*toxicity
MH  - HLA-DQ Antigens/*genetics/metabolism
MH  - Humans
MH  - Liver/enzymology
MH  - *Membrane Proteins
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Receptors, Antigen, T-Cell, alpha-beta/metabolism
MH  - Shock, Septic/*etiology/immunology/mortality
MH  - Streptococcal Infections/etiology/prevention & control
MH  - Streptococcal Vaccines/administration & dosage/immunology
MH  - Streptococcus pyogenes/immunology
MH  - Superantigens/immunology/*toxicity
MH  - T-Lymphocytes/immunology
MH  - Transgenes
EDAT- 2002/08/27 10:00
MHDA- 2002/09/18 10:01
CRDT- 2002/08/27 10:00
PHST- 2002/02/07 00:00 [received]
PHST- 2002/04/22 00:00 [revised]
PHST- 2002/08/27 10:00 [pubmed]
PHST- 2002/09/18 10:01 [medline]
PHST- 2002/08/27 10:00 [entrez]
AID - JID020130 [pii]
AID - 10.1086/341828 [doi]
PST - ppublish
SO  - J Infect Dis. 2002 Aug 15;186(4):501-10. doi: 10.1086/341828. Epub 2002 Jul 19.