CD8(-CELLS CONTROL TH2-DRIVEN PATHOLOGY DURING PULMONARY RESPIRATORY SYNCYTIAL VIRUS-INFECTION() T)

BALB/c mice vaccinated with vaccinia virus expressing the major surfac e glycoprotein G of respiratory syncytial virus (RSV) develop lung eos inophilia during RSV challenge. The G protein is remarkable in that it induces CD4(+), but no CD8(+) T cells in this mouse strain. Studies u sing passive T cell transfers show that co-injection of CD8(+) T cells greatly reduces the Th2-driven lung eosinophilia caused by G-specific CD4(+) T cells. By contrast, vaccination with the fusion protein (F) induces both CD8(+) and CD4(+) T cells, but not lung eosinophilia duri ng RSV infection. These observations suggest that CD8(+) T cells play a crucial role in preventing Th2-driven pathology. We therefore deplet ed mice with anti-CD8 antibodies in vivo. This treatment allowed lung eosinophilia to develop in F-primed mice. Depletion of interferon (IFN )-gamma had a similar effect, suggesting that secretion of this cytoki ne is the mechanism by which CD8(+) T cells exert their effect. To tes t whether similar effects occurred in other strains of mice, RSV-infec ted C57BL/6 mice (which do not develop eosinophilia after sensitizatio n to G) were treated with anti-IFN-gamma. Again, these mice developed eosinophilia. In this strain, genetic deletion of CD8-alpha, beta 2-mi croglobulin or genes coding for the transporter associated with antige n presentation (which in each case eliminates CD8(+) T cells) caused l ung eosinophilia during RSV infection. These studies show the critical roles that CD8(+) T cells and IFN-gamma production play in regulating Th2-driven eosinophilia and provide a unifying explanation for previo us studies of lung eosinophilia. We propose that vaccines designed to enhance CD8(+) T cell recognition might avoid disease caused by CD4(+) Th2 cells.