HLA-DR3 transgenic mice expressing Nur77-GFP reveal early and robust activation of T cells by superantigens during Staphylococcus aureus pneumonia.
2016
The role of superantigens (SAg) in the immunopathogenesis Staphylococcus aureus pneumonia has been shown by several indirect means. To directly demonstrate activation of T cells in vivo during staphylococcal pneumonia by SAg and to study the kinetics of T cell activation, HLA-DR3 + .Nur77-eGFP + mice were used. In these mice, rapid expression of green fluorescent protein (GFP) in T cells occurs only upon activation through the TCR, but not following other inflammatory stimuli. Experimental pneumonia was induced using isogenic strains of S. aureus either producing the SAg staphylococcal enterotoxin B (SEB), or not producing any SAg. Mice were sacrificed at different time points and expression of GFP was determined by flow cytometry. As SEB primarily activates CD4 + and CD8 + T cells bearing TCR Vβ8, the expression of GFP within the TCR Vβ8 + sub-populations was examined. Strong upregulation of GFP in the TCR Vβ8 + sub-population was appreciable in both CD4 + and CD8 + T cell subsets (20–25%) even as early as 4 hours only in mice infected with S. aureus strain producing SEB (SEB+SA), but not those infected with the isogenic strain that does not produce SEB (SEB-SA). Serum cytokine/chemokine levels mirrored this finding. By 24 hours, 80–90% of the CD4 + and CD8 + T cells bearing TCR Vβ8 + expressed GFP in mice infected with SEB+SA, compared to only 1–2% in mice infected with SEB-SA. The pattern of expression of CD69 expression, an early T cell activation marker, was distinct from that of GFP. Our novel study directly demonstrated T cell activation and established their activation kinetics in vivo during staphylococcal pneumonia. These results might be useful for timing of administration of novel drugs aimed at suppressing T cell activation during pneumonia.
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