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By
From the * Beirne B. Carter Center for Immunology Research, and the T lymphocytes play a pivotal role in the immune response during viral infections. In a murine
model of experimental respiratory syncytial virus (RSV) infection, mice sensitized to either of the two major glycoproteins of RSV develop distinct patterns of cytokine secretion and lung
inflammation upon subsequent RSV infection. Mice sensitized to RSV-G (attachment) glycoprotein exhibit a strong interleukin (IL)-4 and IL-5 response and develop pulmonary eosinophilia, whereas mice sensitized to RSV-F (fusion) glycoprotein develop a predominantly T
helper cell (Th)1 response and pulmonary inflammation characterized by mononuclear cell infiltration. In this study, we examined the potential role of virus-specific CD8+ T cytolytic T cells
on the differentiation and activation of functionally distinct CD4+ T cells specific to these viral
glycoproteins. Mice primed with recombinant vaccinia virus expressing RSV-F glycoprotein
mounted a strong RSV-specific, MHC class I-restricted cytolytic response, whereas priming
with recombinant vaccinia virus expressing RSV-G glycoprotein failed to elicit any detectable
cytolytic response. Priming for a RSV-specific CD8+ T cell response, either with a recombinant vaccinia virus expressing RSV-G glycoprotein in which a strong CD8+ T cell epitope
from RSV-M2 (matrix) protein has been inserted or with a combination of vaccinia virus expressing the matrix protein and the RSV-G glycoprotein, suppressed the eosinophil recruitment into the lungs of these mice upon subsequent challenge with RSV. This reduction in
pulmonary eosinophilia correlated with the suppression of Th2 type cytokine production. The
importance of CD8+ T cells in this process was further supported by the results in CD8+ T cell
deficient, Department of Pediatrics, § Department of Microbiology, and Department of Pathology, University of Virginia Health Sciences
Center, Charlottesville, Virginia 22908
2 microglobulin KO mice. In these mice, priming to RSV-F glycoprotein (which
in normal mice primed for a strong cytolytic response and a pulmonary infiltrate consisting
primarily of mononuclear cells on RSV challenge) resulted in the development of marked pulmonary eosinophilia that was not seen in mice with an intact CD8+ T cell compartment.
These results indicate that CD8+ T cells may play an important role in the regulation of the
differentiation and activation of Th2 CD4+ T cells as well as the recruitment of eosinophils
into the lungs during RSV infection.
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