Respiratory Syncytial Virus Interferon Antagonist NS1 Protein Suppresses and Skews the Human T Lymphocyte Response
Figure 5
The NS1 protein affects the polarization of CD4+ T cells.
A, B. The NS1 protein shifts the phenotype of CD4+ T cells towards Th2. A. Percentages of proliferating CD4+ T cells positive for the indicated markers of activation after co-culture with autologous DC that had been pre-infected with the ΔNS1 (red), ΔNS2, and ΔNS1/2 (red) deletion mutants, as compared to the cells from the same donors co-cultivated with DC pre-infected with wt RSV (assigned a value of 100%, doted line). B. Examples of primary flow cytometry data using cells from one representative donor, with the percentage of each population indicated. C, D. The NS1 protein reduces activation and proliferation of Th17 cells. C. Percentages of proliferating CD4+ T cells positive for the indicated markers of activation after co-culture with autologous DC that had been pre-infected with the indicated virus, as compared to wt RSV in cells from the same donor as 100%. D. Examples of primary flow cytometry data using cells from one representative donor, with the percentage of each population indicated. In A-D, cells co-cultivated with mock-infected DC were not analyzed due to the near-absence of proliferation (see Fig. 4). In addition, duplicate of wt RSV co-cultures were prepared containing 133 IU/ml each of exogenously added IFNα2a and IFNβ. In A and C, the markers of activation that were analyzed are indicated on the top of each panel. A total of 8 donors were analyzed, represented by individual symbols, and the horizontal bars indicate mean values. In each panel, the amount of each subpopulation as a percentage of the total proliferating CD4+ T cells is shown for wt RSV. For the ΔNS1 and ΔNS1/2 viruses, the statistical significance of the difference to wt RSV is indicated in blue as follows: a, P<0.05; b, P<0.01, c, P<0.001.