Long-Term Staphylococcal Enterotoxin C1 Exposure Induces Soluble Factor-Mediated Immunosuppression by Bovine CD4 + and CD8 + T Cells

Abstract

Regulatory T cells (T _regs ) help control the development and maintenance of protective immunity and can lead to aberrant immune responses to some pathogens. Several lines of evidence suggest that T _regs are induced by exposure to superantigens (SAgs) in vitro or in vivo. In this study, bovine peripheral blood mononuclear cells (PBMC) were exposed in vitro to a relatively low dose (5 ng/ml) of staphylococcal enterotoxin C1 (SEC1) for up to 10 days. Upon stimulation, CD4 ⁺ and CD8 ⁺ T cells initially proliferated at similar rates. Subsequently, from days 6 through 10, most CD4 ⁺ and CD8 ⁺ T cells proliferated regardless of Vβ specificity, but the proliferation of CD8 ⁺ T cells occurred more vigorously. The transcription of CD25 and CD152 genes increased, whereas that of interleukin-2 (IL-2) decreased. γδ T cells appeared to be unresponsive. An increase in the transcription of IL-10 and transforming growth factor β (TGF-β) genes in SEC1-stimulated cultures was attributed to the CD4 ⁺ CD25 ⁺ T-cell subpopulation. The expression of Foxp3 mRNA also increased and was accompanied by the upregulation of CD152 and the downregulation of IL-2 transcription, suggesting that cells in this subpopulation are T _regs . Functionally, SEC1-stimulated CD4 ⁺ T cells suppressed the proliferation of naive PBMC in response to heat-killed-fixed Staphylococcus aureus . The suppression was partially mediated by IL-10 and TGF-β, another characteristic of certain types of T _regs. The CD8 ⁺ T-cell population also suppressed naive PBMC through another mechanism not mediated by IL-10 or TGF-β. These results provide further insight into the potential mechanisms by which SAgs could contribute to evasion of the immune response, affecting the outcome of infection or colonization.