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

Abstract

Regulatory T cells (Tregs) 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 Tregs 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 Vß 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. T cells appeared to be unresponsive. An increase in the transcription of IL-10 and transforming growth factor ß (TGF-ß) 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 Tregs. 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-ß, another characteristic of certain types of Tregs. The CD8+ T-cell population also suppressed naive PBMC through another mechanism not mediated by IL-10 or TGF-ß. 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.