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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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VG22K effectively primes for RSV-specific memory T lymphocyte response. Splenocytes from mice previously primed with VG or  VG22K were stimulated in vitro with RSV-infected naive spleen cells.  Supernatants were collected 48 h later and analyzed for IL-2, IL-4, IL-5,  and IFN-γ. IL-4 and IL-5 were not detected in culture supernatants from  either group of animals (data not shown).
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Figure 7: VG22K effectively primes for RSV-specific memory T lymphocyte response. Splenocytes from mice previously primed with VG or VG22K were stimulated in vitro with RSV-infected naive spleen cells. Supernatants were collected 48 h later and analyzed for IL-2, IL-4, IL-5, and IFN-γ. IL-4 and IL-5 were not detected in culture supernatants from either group of animals (data not shown).

Mentions: To further establish that the G/22K can efficiently prime an RSV-specific memory T lymphocyte response, we examined the cytokine response of immune splenocytes from VG- and VG22K-primed mice to in vitro stimulation with RSV. As Fig. 7 shows, G-immune and G/22K-immune splenocytes produced comparable levels of IL-2 in response to RSV suggesting that the wild-type G and the chimeric G/22K proteins induced a comparable expansion of IL-2– producing memory T lymphocytes. It is also noteworthy that neither G/22K- nor G-immune splenocyte cultures produced detectable IL-4 or IL-5 after a single cycle of in vitro stimulation with RSV (data not shown). This result is consistent with our earlier findings that RSV-specific memory CD4+ T lymphocytes in the spleen, unlike the polarized effector populations found in the lung after RSV infection, produce predominantly IL-2 and IFN-γ after the first in vitro stimulation with antigen (14). The high level of IFN-γ produced by immune splenocytes from mice primed with VG22K most likely reflects the activation of 22K-specific CD8+ T cells in these bulk cultures.


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)

VG22K effectively primes for RSV-specific memory T lymphocyte response. Splenocytes from mice previously primed with VG or  VG22K were stimulated in vitro with RSV-infected naive spleen cells.  Supernatants were collected 48 h later and analyzed for IL-2, IL-4, IL-5,  and IFN-γ. IL-4 and IL-5 were not detected in culture supernatants from  either group of animals (data not shown).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 7: VG22K effectively primes for RSV-specific memory T lymphocyte response. Splenocytes from mice previously primed with VG or VG22K were stimulated in vitro with RSV-infected naive spleen cells. Supernatants were collected 48 h later and analyzed for IL-2, IL-4, IL-5, and IFN-γ. IL-4 and IL-5 were not detected in culture supernatants from either group of animals (data not shown).
Mentions: To further establish that the G/22K can efficiently prime an RSV-specific memory T lymphocyte response, we examined the cytokine response of immune splenocytes from VG- and VG22K-primed mice to in vitro stimulation with RSV. As Fig. 7 shows, G-immune and G/22K-immune splenocytes produced comparable levels of IL-2 in response to RSV suggesting that the wild-type G and the chimeric G/22K proteins induced a comparable expansion of IL-2– producing memory T lymphocytes. It is also noteworthy that neither G/22K- nor G-immune splenocyte cultures produced detectable IL-4 or IL-5 after a single cycle of in vitro stimulation with RSV (data not shown). This result is consistent with our earlier findings that RSV-specific memory CD4+ T lymphocytes in the spleen, unlike the polarized effector populations found in the lung after RSV infection, produce predominantly IL-2 and IFN-γ after the first in vitro stimulation with antigen (14). The high level of IFN-γ produced by immune splenocytes from mice primed with VG22K most likely reflects the activation of 22K-specific CD8+ T cells in these bulk cultures.

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