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, we depleted Tregs in BALB/c mice by injecting anti-CD25 antibody followed by RSV infection (anti-CD25-RSV mice). RESULTS: In this model, decrease of anti-fusion (F) antibody and neutralizing activity but increase of anti-nucleocapsid (N) antibody in serum were seen. We also observed decreased ADCC activity, increased IgG2a, and influx of activated CD8+ T cells into the lungs. 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. Inclusion of CD25+ Treg cells isolated from isotype Ig-RSV mice into the B/CD4 co-culture substantially enhanced the frequency of anti-F antibody production. But 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 obtained from anti-CD25-RSV mice. 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 Treg cells modulate B cell activity, particularly in producing F-specific neutralizing antibodies, to regulate RSV-mediated exacerbated diseases.
Date:
2015-12
Relation:
International Journal of Infectious Diseases. 2015 Dec;41:56-64.
