Critical role of T cell migration in bacterial superantigen-mediated shock in mice.
Bacterial superantigens have been implicated in the pathogenesis of several human diseases. Among them, toxic shock syndrome (TSS) is a prototypic acute intoxication caused by the pyrogenic exotoxin family of superantigens. In this study, we investigated the pathophysiological mechanism of TSS using the Yersinia pseudotuberculosis-derived mitogen (YPM) and its point mutants. The results indicated that YPM could induce toxic shock in BALB/c mice but not in T cell-deficient SCID mice. We found that Vbeta8(+) T cells activated by YPM migrated from peripheral blood to liver as early as 1 h after injection of YPM and that serum level of IFN-gamma was significantly elevated 4 h after YPM injection. Co-administration of anti-IFN-gamma antibody or anti-YPM monoclonal antibody alleviated the liver injury and protected mice from YPM-induced death. Moreover, anti-YPM antibody also suppressed the early migration of Vbeta8(+) T cells from the peripheral circulation and the elevation of serum IFN-gamma level, indicating a pivotal role of T cells in inducing shock in our mouse model.
Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
Hirotsugu
H
Kano
Yasuhiko
Y
Ito
Kentaro
K
Matsuoka
Toshiharu
T
Nakajima
Tsutomu
T
Iwata
Takao
T
Kohsaka
Hirohisa
H
Saito
Jun
J
Abe
D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D005260:Female; D006651:Histocytochemistry; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D008099:Liver / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D017354:Point Mutation; D012772:Shock, Septic / Q000276:immunology* / Q000473:pathology; D013154:Spleen / Q000276:immunology / Q000473:pathology; D018089:Superantigens / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015011:Yersinia pseudotuberculosis / Q000276:immunology*; D015012:Yersinia pseudotuberculosis Infections / Q000276:immunology* / Q000473:pathology
D001426:Bacterial Proteins; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; C093313:Yersinia pseudotuberculosis-derived mitogen; D016753:Interleukin-10; D007371:Interferon-gamma