Depletion of regulatory T-cells leads to moderate B-cell antigenicity in respiratory syncytial virus infection.

OBJECTIVES:The regulation of the immunopathology of respiratory syncytial virus (RSV) by regulatory T-cells (CD4(+)CD25(+)Foxp3(+); Tregs) is not understood. METHODS:To deduce the same, Tregs were depleted in BALB/c mice by injecting anti-CD25 antibody followed by RSV infection (anti-CD25-RSV mice). RESULTS:In this model, a decrease in anti-fusion (F) antibody and neutralizing activity, and an increase in anti-nucleocapsid (N) antibody in serum, were seen. Decreased antibody-dependent cell-mediated cytotoxicity (ADCC) activity, increased IgG2a, and an influx of activated CD8(+) T-cells into the lungs were also observed. Co-culture of splenic CD45RA(+) B-cells from RSV-infected normal mice with CD4(+) cells isolated from anti-CD25-RSV mice (B/CD4) increased anti-F antibody secretion. The inclusion of CD25(+) Tregs isolated from isotype Ig-RSV mice into the B/CD4 co-culture substantially enhanced the frequency of anti-F antibody production. However, the same effect was not seen in the co-culture of CD45RA(+) B-cells with dendritic cells (DCs) (B/DCs) or CD8(+) cells (B/CD8) that were obtained from anti-CD25-RSV mice. The transfer of enriched B-cells from anti-CD25-RSV mice into RSV-infected SCID mice increased severe lung inflammation associated with the increased viral load and eosinophil number. CONCLUSIONS:These results indicate that Tregs modulate B-cell activity, particularly in producing F-specific neutralizing antibodies, to regulate RSV-mediated exacerbated diseases.