Pulmonary eosinophilia is attenuated by early responding CD8(+) memory T cells in a murine model of RSV vaccine-enhanced disease.
Vaccination with formalin-inactivated respiratory syncytial virus (RSV) vaccine results in enhanced respiratory tract inflammation and injury following subsequent RSV infection. RSV vaccine-enhanced disease can also be produced in mice by prior vaccination with a vaccinia virus vector containing the RSV G protein, followed by intranasal infectious RSV challenge, a process characterized by induction of a potent memory CD4(+) T-cell response to challenge infection with some features characteristic of Th-2 CD4(+) T-cell responses, including increased eosinophil accumulation in pulmonary inflammatory infiltrates. The adaptive immune response to the RSV G protein in immunized BALB/c mice is characterized by a weak or absent primary and secondary recall CD8(+) T-cell response. These and related results have led to the hypothesis that the failure of the infected animals to mount an effective CD8(+) memory T-cell (CD8(+) Tm) response in this model could account for the pulmonary eosinophilia associated with the development of enhanced disease, and that CD8(+) T cells may control the development of eosinophilia. In this study, we investigated how and when the generation of a CD8(+) Tm response to RSV infection might affect the development of pulmonary eosinophilia in this model of vaccine-enhanced disease. By defining the CD8(+) T-cell response kinetics and monitoring lung parenchymal eosinophil accumulation, we show that the establishment of an RSV-specific CD8(+) Tm response in the infected lungs early after challenge infection (i.e., within the first 3 d of RSV infection) is necessary and sufficient to control pulmonary eosinophilia development. Additionally, our work suggests that the mechanism by which CD8(+) T cells regulate this process is not by modulating the differentiation or development of the CD4(+) Tm response. Rather, we demonstrate that IL-10 produced by early responding CD8(+) Tm cells may regulate the pulmonary eosinophilia development observed in RSV vaccine-enhanced disease.
Stevens
Whitney W
WW
Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia 22908, USA.
Sun
Jie
J
Castillo
Jonathan P
JP
Braciale
Thomas J
TJ
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D005260:Female; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D011657:Pulmonary Eosinophilia / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000150:complications / Q000276:immunology* / Q000517:prevention & control; D022261:Respiratory Syncytial Virus Vaccines / Q000276:immunology* / Q000627:therapeutic use; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology; D013997:Time Factors; D015164:Vaccines, Inactivated / Q000276:immunology / Q000627:therapeutic use
D022261:Respiratory Syncytial Virus Vaccines; D015164:Vaccines, Inactivated; D016753:Interleukin-10