Regulatory T cells modulate granulomatous inflammation in an HLA-DP2 transgenic murine model of beryllium-induced disease.
Proc Natl Acad Sci U S A
; 111(23): 8553-8, 2014 Jun 10.
Article
em En
| MEDLINE
| ID: mdl-24912188
ABSTRACT
Susceptibility to chronic beryllium disease (CBD) is linked to certain HLA-DP molecules, including HLA-DP2. To elucidate the molecular basis of this association, we exposed mice transgenic (Tg) for HLA-DP2 to beryllium oxide (BeO) via oropharyngeal aspiration. As opposed to WT mice, BeO-exposed HLA-DP2 Tg mice developed mononuclear infiltrates in a peribronchovascular distribution that were composed of CD4(+) T cells and included regulatory T (Treg) cells. Beryllium-responsive, HLA-DP2-restricted CD4(+) T cells expressing IFN-γ and IL-2 were present in BeO-exposed HLA-DP2 Tg mice and not in WT mice. Using Be-loaded HLA-DP2-peptide tetramers, we identified Be-specific CD4(+) T cells in the mouse lung that recognize identical ligands as CD4(+) T cells derived from the human lung. Importantly, a subset of HLA-DP2 tetramer-binding CD4(+) T cells expressed forkhead box P3, consistent with the expansion of antigen-specific Treg cells. Depletion of Treg cells in BeO-exposed HLA-DP2 Tg mice exacerbated lung inflammation and enhanced granuloma formation. These findings document, for the first time to our knowledge, the development of a Be-specific adaptive immune response in mice expressing HLA-DP2 and the ability of Treg cells to modulate the beryllium-induced granulomatous immune response.
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MEDLINE
Assunto principal:
Beriliose
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Linfócitos T Reguladores
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Modelos Animais de Doenças
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Cadeias beta de HLA-DP
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Granuloma
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Inflamação
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article