Staphylococcal Enterotoxin B (SEB) Induces Memory CD4 T Cell Anergy in vivo and Impairs Recall Immunity to Unrelated Antigens.

David K Janik William T Lee

doi:10.4172/2155-9899.1000346

Abstract

IntroductionNaïve 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 cells in vivo and 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.MethodBALB/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.ResultsComparing 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.ConclusionThe present study indicated that SEB selectively targeted memory CD4 T cells in vivo and prevented helper function. Consequently, recall humoral immunity was lost. The data are most consistent with in vivo T 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.

Highlights

Naïve and memory T cells can utilize unique regulatory pathways to promote protection but prevent self-reactivity
The present study indicated that SEB selectively targeted memory CD4 T cells in vivo and prevented helper function
The data are most consistent with in vivo T cell anergy as opposed to indirect suppression as elimination of Fyn kinase restored helper function. These data suggest that bacterial superantigens can impair postvaccination memory cell responses to unrelated antigens via their ability to target Vb families and antagonize memory cell activation

Summary

Introduction

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. We evaluated Ab responses to a T-dependent antigen as a measurement of memory T cell helper function. An initial encounter with foreign antigen stimulates T lymphocyte proliferation and differentiation into “antigen experienced” effector and memory cells. Memory cells may be activated more quickly due to altered requirements for costimulation, increased adhesion marker expression and, possibly, an increased sensitivity of signaling through the antigen receptor [6,7]. Improper responses against self-antigens by memory cells must be prevented. It is likely that memory cells utilize additional or different regulatory mechanisms to prevent inappropriate activation

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