Limits...
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.

Show MeSH

Related in: MedlinePlus

Cytokines produced by cells isolated from lungs of mice  primed with recombinant vaccinia virus and challenged with RSV. Mice  were primed with indicated recombinant vaccinia virus and challenged  with live RSV intranasally 3 wk after priming. Mononuclear cells were  isolated from lungs of these mice 5 d after challenge and stimulated with  RSV. Supernatants were collected 48 h later and analyzed for cytokines  by ELISA.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2198992&req=5

Figure 6: Cytokines produced by cells isolated from lungs of mice primed with recombinant vaccinia virus and challenged with RSV. Mice were primed with indicated recombinant vaccinia virus and challenged with live RSV intranasally 3 wk after priming. Mononuclear cells were isolated from lungs of these mice 5 d after challenge and stimulated with RSV. Supernatants were collected 48 h later and analyzed for cytokines by ELISA.

Mentions: We previously reported that antigen-dependent cytokine production by mononuclear cells isolated at day 5 after intranasal RSV challenge from the lungs of RSV-F– or RSV-G–primed mice directly correlates with the type of pulmonary inflammatory response demonstrable histologically in these primed animals at day 5 after RSV challenge (14). Thus, lung mononuclear cells isolated from infected G-primed mice secreted high levels of IL-4 and particularly IL-5 commensurate with the eosinophil accumulation in the lungs of these animals. A similar analysis was carried out on lung mononuclear cells from RSV-challenged mice primed with VF, VG, or VG22K. Fig. 6 showed the cytokine production by mononuclear cells isolated from the lungs of these animals in response to RSV stimulation in vitro. As reported previously (14), cells isolated from the VF-primed animals produced high levels of IL-2 and IFN-γ. Consistent with the histologic findings reported above (Fig. 5), cells isolated from mice primed with VG, on the other hand, secreted high levels of IL-4 and IL-5. Low but detectable levels of IL-4 and IL-5 were found in the culture supernatants of lung cell cultures from VF-primed animals. Also consistent with the histologic finding, the levels of the Th2 type cytokines (IL-4 and IL-5) produced by infiltrating lung mononuclear cells from mice primed with VG22K were markedly lower than the levels produced by cells from mice primed with recombinant vaccinia virus expressing the native RSV-G glycoprotein and were comparable to the levels detected in the VF-primed animals. IFN-γ production by lung mononuclear cells were comparable among mice primed with G, G22K, or F. As expected, cells isolated from the lungs of RSV-infected mice primed with the control recombinant vaccinia (VCS11) produced low or nondetectable levels of all cytokines.


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)

Cytokines produced by cells isolated from lungs of mice  primed with recombinant vaccinia virus and challenged with RSV. Mice  were primed with indicated recombinant vaccinia virus and challenged  with live RSV intranasally 3 wk after priming. Mononuclear cells were  isolated from lungs of these mice 5 d after challenge and stimulated with  RSV. Supernatants were collected 48 h later and analyzed for cytokines  by ELISA.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 6: Cytokines produced by cells isolated from lungs of mice primed with recombinant vaccinia virus and challenged with RSV. Mice were primed with indicated recombinant vaccinia virus and challenged with live RSV intranasally 3 wk after priming. Mononuclear cells were isolated from lungs of these mice 5 d after challenge and stimulated with RSV. Supernatants were collected 48 h later and analyzed for cytokines by ELISA.
Mentions: We previously reported that antigen-dependent cytokine production by mononuclear cells isolated at day 5 after intranasal RSV challenge from the lungs of RSV-F– or RSV-G–primed mice directly correlates with the type of pulmonary inflammatory response demonstrable histologically in these primed animals at day 5 after RSV challenge (14). Thus, lung mononuclear cells isolated from infected G-primed mice secreted high levels of IL-4 and particularly IL-5 commensurate with the eosinophil accumulation in the lungs of these animals. A similar analysis was carried out on lung mononuclear cells from RSV-challenged mice primed with VF, VG, or VG22K. Fig. 6 showed the cytokine production by mononuclear cells isolated from the lungs of these animals in response to RSV stimulation in vitro. As reported previously (14), cells isolated from the VF-primed animals produced high levels of IL-2 and IFN-γ. Consistent with the histologic findings reported above (Fig. 5), cells isolated from mice primed with VG, on the other hand, secreted high levels of IL-4 and IL-5. Low but detectable levels of IL-4 and IL-5 were found in the culture supernatants of lung cell cultures from VF-primed animals. Also consistent with the histologic finding, the levels of the Th2 type cytokines (IL-4 and IL-5) produced by infiltrating lung mononuclear cells from mice primed with VG22K were markedly lower than the levels produced by cells from mice primed with recombinant vaccinia virus expressing the native RSV-G glycoprotein and were comparable to the levels detected in the VF-primed animals. IFN-γ production by lung mononuclear cells were comparable among mice primed with G, G22K, or F. As expected, cells isolated from the lungs of RSV-infected mice primed with the control recombinant vaccinia (VCS11) produced low or nondetectable levels of all cytokines.

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