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Virus-specific CD8+ T lymphocytes downregulate T helper cell type 2 cytokine secretion and pulmonary eosinophilia during experimental murine respiratory syncytial virus infection.

Srikiatkhachorn A, Braciale TJ - J. Exp. Med. (1997)

Bottom Line: 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.This reduction in pulmonary eosinophilia correlated with the suppression of Th2 type cytokine production.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.

View Article: PubMed Central - PubMed

Affiliation: Beirne B. Carter Center for Immunology Research, University of Virginia Health Sciences Center, Charlottesville 22908, USA. as7a@virginia.edu

ABSTRACT
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, beta 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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Lung histopathology of β2mKO  mice sensitized to RSV glycoproteins. Mice  were primed with VG (A), VF (B), or VSC11  (C) and challenged with live RSV intranasally 3  wk after priming. Mice were killed 5 d after  challenge, and lung sections were stained for  eosinophils with Leinert-Giemsa stain. Original  magnification: 200.
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Figure 9: Lung histopathology of β2mKO mice sensitized to RSV glycoproteins. Mice were primed with VG (A), VF (B), or VSC11 (C) and challenged with live RSV intranasally 3 wk after priming. Mice were killed 5 d after challenge, and lung sections were stained for eosinophils with Leinert-Giemsa stain. Original magnification: 200.

Mentions: The findings so far suggest that the induction of a memory CD8+ T lymphocyte response to RSV suppresses lung eosinophilia and downregulates IL-4 and IL-5 production in RSV-G immune mice after intranasal RSV challenge. If this is the case, then priming to either RSV-F or RSV-G in CD8+ T cell–deficient mice should result in enhanced pulmonary eosinophilia with RSV challenge. Figs. 9 and 10 show the results of this analysis carried out in β2m-deficient (β2mKO) mice.


Virus-specific CD8+ T lymphocytes downregulate T helper cell type 2 cytokine secretion and pulmonary eosinophilia during experimental murine respiratory syncytial virus infection.

Srikiatkhachorn A, Braciale TJ - J. Exp. Med. (1997)

Lung histopathology of β2mKO  mice sensitized to RSV glycoproteins. Mice  were primed with VG (A), VF (B), or VSC11  (C) and challenged with live RSV intranasally 3  wk after priming. Mice were killed 5 d after  challenge, and lung sections were stained for  eosinophils with Leinert-Giemsa stain. Original  magnification: 200.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2198992&req=5

Figure 9: Lung histopathology of β2mKO mice sensitized to RSV glycoproteins. Mice were primed with VG (A), VF (B), or VSC11 (C) and challenged with live RSV intranasally 3 wk after priming. Mice were killed 5 d after challenge, and lung sections were stained for eosinophils with Leinert-Giemsa stain. Original magnification: 200.
Mentions: The findings so far suggest that the induction of a memory CD8+ T lymphocyte response to RSV suppresses lung eosinophilia and downregulates IL-4 and IL-5 production in RSV-G immune mice after intranasal RSV challenge. If this is the case, then priming to either RSV-F or RSV-G in CD8+ T cell–deficient mice should result in enhanced pulmonary eosinophilia with RSV challenge. Figs. 9 and 10 show the results of this analysis carried out in β2m-deficient (β2mKO) mice.

Bottom Line: 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.This reduction in pulmonary eosinophilia correlated with the suppression of Th2 type cytokine production.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.

View Article: PubMed Central - PubMed

Affiliation: Beirne B. Carter Center for Immunology Research, University of Virginia Health Sciences Center, Charlottesville 22908, USA. as7a@virginia.edu

ABSTRACT
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, beta 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.

Show MeSH
Related in: MedlinePlus