The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/8/421/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 3, August 4, 1997 421-432


Articles

Virus-specific CD8+ T Lymphocytes Downregulate T Helper Cell Type 2 Cytokine Secretion and Pulmonary Eosinophilia during Experimental Murine Respiratory Syncytial Virus Infection

Anon Srikiatkhachorn*,{ddagger} and Thomas J. Braciale*,§,||

From the * Beirne B. Carter Center for Immunology Research, and the {ddagger} Department of Pediatrics, § Department of Microbiology, and || Department of Pathology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908

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, β2 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.


Address correspondence to Dr. Anon Srikiatkhachorn, University of Virginia Health Sciences Center, MR4, Rm 4012, Charlottesville, VA 22908. Phone: 804-924-1278; FAX 804-924-1221; E-mail: as7a{at}virginia.edu

1 Abbreviations used in this paper: β2m, β2 microglobulin; G22K, portion of cDNA encoding the G protein with inserted 22K epitope; RSV, respiratory syncytial virus; V22K, recombinant vaccinia virus expressing RSV matric (M2 or 22K) protein; VF, recombinant vaccinia virus expressing RSV fusion glycoprotein; VG, recombinant vaccinia virus expressing RSV attachment glycoprotein; VG22K, recombinant vaccinia virus expressing chimeric G/22K glycoprotein.


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