VIRUS-SPECIFIC CD8(-LYMPHOCYTES DOWN-REGULATE T-HELPER CELL-TYPE-2 CYTOKINE SECRETION AND PULMONARY EOSINOPHILIA DURING EXPERIMENTAL MURINERESPIRATORY SYNCYTIAL-VIRUS-INFECTION() T)

T lymphocytes play a pivotal role in the immune response during viral infections. In a murine model of experimental respiratory syncytial vi rus (RSV) infection, mice sensitized to either of the two major glycop roteins of RSV develop distinct patterns of cytokine secretion and lun g 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 v irus-specific CD8(+) T cytolytic T cells on the differentiation and ac tivation of functionally distinct CD4(+) T cells specific to these vir al glycoproteins. Mice primed with recombinant vaccinia virus expressi ng RSV-F glycoprotein mounted a strong RSV-specific, MHC class I-restr icted cytolytic response, whereas priming with recombinant vaccinia vi rus expressing RSV-G glycoprotein failed to elicit any detectable cyto lytic response. Priming for a RSV-specific CD8(+) T cell response, eit her 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 r ecruitment into the lungs of these mice upon subsequent challenge with RSV. This reduction in pulmonary eosinophilia correlated with the sup pression of Th2 type cytokine production. The importance of CD8(+) T c ells in this process was further supported by the results in CD8(+) T cell deficient, beta(2) microglobulin KO mice. In these mice, priming to RSV-F glycoprotein (which in normal mice primed for a strong cytoly tic response and a pulmonary infiltrate consisting primarily of mononu clear cells on RSV challenge) resulted in the development of marked pu lmonary 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 activa tion of Th2 CD4(+) T cells as well as the recruitment of eosinophils i nto the lungs during RSV infection.