title: Staphylococcal Enterotoxin B (SEB) Induces Memory CD4 T Cell Anergyin vivoand Impairs Recall Immunity to Unrelated Antigens.
abstract: BACKGROUND
  Naïve and memory T cells can utilize unique regulatory pathways to promote protection but prevent self-reactivity. A bacterial superantigen SEB exploits unique TCR proximal signaling processes in memory CD4 T cells to induce clonal anergy. The aim of this study was to determine if SEB could antagonize memory CD4 T cellsin vivoand whether there would be consequences on recall immune responses. We evaluated Ab responses to a T-dependent antigen as a measurement of memory T cell helper function.
  
  
  METHODS
  BALB/c mice were primed with TNP-RGG to elicit memory B cells and also immunized with an ovalbumin peptide to elicit memory helper T cells. Another group of TNP-RGG immunized mice were used as adoptive transfer recipients of exogenous DO11.10 memory T cells. Mice were challenged with TNP-OVA with or without prior administration of SEB. B cells secreting IgM or IgG TNP-specific Ab were enumerated by ELISPOT as indicators of primary versus secondary humoral immunity.
  
  
  RESULTS
  Comparing the SEB and non-SEB-treated groups, the SEB-treated group failed to produce TNP-specific IgG in response to challenge with TNP-OVA, even if they were previously immunized with OVA. All groups produced IgM, indicating that the primary Ab responses and naïve helper T cells were not impacted by SEB. SEB had no negative impact when DO11.10 × Fyn-/-memory T cells were used as donor cells.
  
  
  CONCLUSIONS
  The present study indicated that SEB selectively targeted memory CD4 T cellsin vivoand prevented helper function. Consequently, recall humoral immunity was lost. The data are most consistent within vivoT cell anergy as opposed to indirect suppression as elimination of Fyn kinase restored helper function. These data suggest that bacterial superantigens can impair post-vaccination memory cell responses to unrelated antigens via their ability to target Vb families and antagonize memory cell activation.
authors.affiliation: The Department of Biomedical Sciences, School of Public Health, The University at Albany, USA.
authors.forename: David K
authors.initials: DK
authors.lastname: Janik
authors.affiliation: The Department of Biomedical Sciences, School of Public Health, The University at Albany, USA; The Laboratory of Immunology, The Wadsworth Center, New York State Department of Health, USA.
authors.forename: William T
authors.initials: WT
authors.lastname: Lee
keywords: Clonal anergy; Helper T cells; Immune tolerance; Immunological memory; Recall immunity; Superantigens; T Lymphocytes