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J Allergy Clin Immunol. 2007 Mar;119(3):671-9.

Skin inflammation in RelB(-/-) mice leads to defective immunity and impaired clearance of vaccinia virus.

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  • 1Department of Pediatrics, Division of Immunology, Children's Hospital, Harvard Medical School, Boston, MA, USA.

Abstract

BACKGROUND:

Atopic dermatitis (AD) is an inflammatory skin disorder occurring in genetically predisposed individuals with a systemic T(H)2 bias. Atopic dermatitis patients exposed to the smallpox vaccine, vaccinia virus (VV), occasionally develop eczema vaccinatum (EV), an overwhelming and potentially lethal systemic infection with VV.

OBJECTIVE:

To establish a murine model of EV and examine the effects of skin inflammation on VV immunity.

METHODS:

The skin of RelB(-/-) mice, like that of chronic AD lesions in humans, exhibits thickening, eosinophilic infiltration, hyperkeratosis, and acanthosis. RelB(-/-) and wild-type (WT) control mice were infected with VV via skin scarification. Viral spread, cytokine levels, IgG2a responses and VV-specific T cells were measured.

RESULTS:

Cutaneously VV-infected RelB(-/-), but not WT mice, exhibited weight loss, markedly impaired systemic clearance of the virus and increased contiguous propagation from the inoculation site. This was associated with a dramatically impaired generation of IFN-gamma-producing CD8(+) vaccinia-specific T cells along with decreased secretion of IFN-gamma by VV-stimulated splenocytes. The T(H)2 cytokines-IL-4, IL-5, IL-13, and IL-10-on the other hand, were overproduced. When infected intraperitoneally, RelB(-/-) mice generated robust T cell responses with good IFN-gamma production.

CONCLUSION:

Allergic inflammation in RelB(-/-) mice is associated with dysregulated immunity to VV encountered via the skin. We speculate that susceptibility of AD patients to overwhelming vaccinia virus infection is similarly related to ineffective T cell responses.

CLINICAL IMPLICATIONS:

The susceptibility of patients with AD to EV following cutaneous contact with VV is related to ineffective antiviral immune responses.

PMID:
17336617
[PubMed - indexed for MEDLINE]
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