Temporal sequence and functional implications of V beta-specific T cell receptor down-regulation and costimulatory molecule expression following in vitro stimulation with the staphylococcal superantigen Toxic shock syndrome toxin-1.
The superantigen toxic shock syndrome toxin-1 (TSST-1) is implicated as the major cause of staphylococcal toxic shock syndrome. The temporal sequence of early signaling events in human peripheral blood mononuclear cells following TSST-1 stimulation was examined. TSST-1 induced rapid and complete down-regulation of V beta 2-specific T cell receptor (TCR), followed by transient CD154 expression on CD4(+) lymphocytes. This was sequentially followed by the up-regulation of CD86, CD80, CD40, and human leukocyte antigen-DR expression on CD14(+) monocytes. In contrast, S14N, a TSST-1 mutant toxin with a single amino acid substitution that is known to be impaired in interleukin (IL)--2, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha secretion, was deficient in both V beta 2-TCR down-regulation and CD154 and CD80/CD86 expression. Furthermore, pretreatment with monoclonal antibodies against V beta 2-TCR, CD80/CD86, and CD154 significantly inhibited TSST-1-induced IL-2, IFN-gamma, and TNF-alpha secretion. Taken together, these results indicate that early V beta-specific TCR activation, along with CD80/CD86 and CD154 costimulation, are key determinants of the TSST-1-induced proinflammatory cytokine response.
Kum
Winnie W S
WW
Department of Medicine, Division of Infectious Diseases, University of British Columbia, Vancouver Hospital, Vancouver, Canada.
Hung
Ryan W Y
RW
Cameron
Scott B
SB
Chow
Anthony W
AW
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis / Q000502:physiology; D018122:B7-1 Antigen / Q000032:analysis / Q000502:physiology; D051940:B7-2 Antigen; D001427:Bacterial Toxins; D018106:CD28 Antigens / Q000032:analysis; D019013:CD40 Antigens / Q000032:analysis / Q000502:physiology; D023201:CD40 Ligand / Q000032:analysis; D016207:Cytokines / Q000096:biosynthesis; D015536:Down-Regulation; D004768:Enterotoxins / Q000494:pharmacology*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis / Q000502:physiology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000502:physiology*; D018089:Superantigens
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D001427:Bacterial Toxins; D018106:CD28 Antigens; D019013:CD40 Antigens; C497964:CD86 protein, human; D016207:Cytokines; D004768:Enterotoxins; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; D023201:CD40 Ligand