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

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.

• Authors: Teresa R Johnson, Marc E Rothenberg, Barney S Graham
• Journal: Journal of leukocyte biology (J Leukoc Biol) Vol. 84 Issue 3 Pg. 748-59 (Sep 2008) ISSN: 0741-5400 [Print] United States
• PMID: 18519743 (Publication Type: Journal Article)

Chemical References

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

Topics

• 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, metabolism)
• Lung (immunology, metabolism, virology)
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• Pulmonary Eosinophilia (immunology, prevention & control, virology)
• Respiratory Syncytial Virus Infections (immunology, pathology, virology)
• Respiratory Syncytial Virus Vaccines (administration & dosage, immunology)
• Respiratory Syncytial Viruses (immunology)
• Vaccinia virus (immunology)
• Viral Fusion Proteins (immunology)
• Viral Load
• Weight Loss