Pulmonary eosinophilia requires interleukin-5, eotaxin-1, and CD4+ T cells in mice immunized with respiratory syncytial virus G glycoprotein

J Leukoc Biol. 2008 Sep;84(3):748-59. doi: 10.1189/jlb.0907621. Epub 2008 Jun 2.

Abstract

Severe illness, type 2 cytokine production, and pulmonary eosinophilia are adverse immune responses resulting from respiratory syncytial virus (RSV) challenge of vvGs-immunized mice. We have shown IL-4 and IL-13 activity must be simultaneously inhibited to reduce disease severity. We now address the contributions of IL-5, eotaxin-1, and CD4+ and CD8+ T cells to the induction of disease-enhancing immune responses. Depletion of CD4+ T cells during immunization prevented IL-4, IL-13, and eotaxin-1 production, diminished eosinophilia, and reduced weight loss. Conversely, CD8+ T cell depletion did not decrease eosinophilia, weight loss, or type 2 cytokines but did dramatically reduce mucus production and increase eotaxin production. Anti-IL-5 administration at immunization or challenge significantly decreased pulmonary eosinophilia. Strikingly, there were not concomitant decreases in weight loss. Following RSV challenge eotaxin-1-deficient mice immunized with vvGs exhibited significantly less eosinophilia without decreased weight loss or type 2 cytokine production. We conclude CD4+ T cell production of IL-5 and induction of eotaxin-1 are required for vvGs-induced eosinophilia following RSV challenge, while CD8+ T cells appear to down-regulate eotaxin-1 and mucus production. In summary, we demonstrate that pulmonary eosinophilia 1) is a by-product of memory CD4+ T cell activation, 2) does not necessarily correlate with mucus production, and, most importantly, 3) is not required for the RSV G-induced illness in mice. These findings have important implications for the evaluation of candidate RSV vaccines.

MeSH terms

  • Animals
  • Bronchoalveolar Lavage
  • CD4-Positive T-Lymphocytes / immunology*
  • Chemokine CCL11 / physiology*
  • Enzyme-Linked Immunosorbent Assay
  • Immunization
  • Interleukin-13 / metabolism
  • Interleukin-4 / metabolism
  • Interleukin-5 / antagonists & inhibitors
  • Interleukin-5 / metabolism*
  • Lung / immunology
  • Lung / metabolism
  • Lung / virology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Pulmonary Eosinophilia / immunology*
  • Pulmonary Eosinophilia / prevention & control
  • Pulmonary Eosinophilia / virology
  • Respiratory Syncytial Virus Infections / immunology*
  • Respiratory Syncytial Virus Infections / pathology
  • Respiratory Syncytial Virus Infections / virology
  • Respiratory Syncytial Virus Vaccines / administration & dosage
  • Respiratory Syncytial Virus Vaccines / immunology
  • Respiratory Syncytial Viruses / immunology*
  • Vaccinia virus / immunology
  • Viral Fusion Proteins / immunology*
  • Viral Load
  • Weight Loss

Substances

  • Ccl11 protein, mouse
  • Chemokine CCL11
  • G glycoprotein, Respiratory syncytial virus
  • Interleukin-13
  • Interleukin-5
  • Respiratory Syncytial Virus Vaccines
  • Viral Fusion Proteins
  • Interleukin-4