Published online before print June 2, 2008
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Article |
,
*Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, USA; and Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA
@ To whom correspondence should be addressed. E-mail: teresaj{at}nih.gov.
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.
Key Words: vaccine • pathogenesis • cytokines • chemokines • immunoregula tion
This article has been cited by other articles:
 |
|
 |
|
  M. R. Olson and S. M. Varga Fas Ligand Is Required for the Development of Respiratory Syncytial Virus Vaccine-Enhanced Disease J. Immunol., March 1, 2009; 182(5): 3024 - 3031. [Abstract] [Full Text] [PDF]
|
|
