Beryllium-induced tumor necrosis factor-alpha production by CD4+ T cells is mediated by HLA-DP.
Am J Respir Cell Mol Biol
; 31(1): 122-30, 2004 Jul.
Article
em En
| MEDLINE
| ID: mdl-14975942
ABSTRACT
Beryllium (Be) presentation to CD4+ T cells from patients with chronic beryllium disease (CBD) results in T cell activation, and these Be-specific CD4+ T cells undergo clonal proliferation and T-helper 1-type cytokine production. In exposed workers, genetic susceptibility to this granulomatous disorder is associated with particular HLA-DPB1 alleles. We hypothesized that these HLA-DP molecules could mediate Be-stimulated tumor necrosis factor-alpha (TNF-alpha) messenger RNA (mRNA) and protein production. Using intracellular cytokine staining, we found that treatment with an anti-HLA-DP, but not anti-HLA-DR, monoclonal antibody inhibited Be-stimulated TNF-alpha expression in lung CD3+ CD4+ T cells. This monoclonal antibody also blocked Be-specific T cell proliferation, increased production of TNF-alpha mature-mRNA transcripts, and increased TNF-alpha protein production by Be-stimulated CBD peripheral blood mononuclear cells and bronchoalveolar lavage (BAL) cells. The Be-stimulated upregulation of TNF-alpha mature-mRNA levels with TNF-alpha protein production was a unique property of CBD BAL cells, and did not occur in BAL cells from Be-sensitized patients without CBD, or sarcoidosis BAL cells. This study identifies HLA-DP as a regulatory component in the activation of T cell receptors on Be-specific CD4+ T cells from CBD patients resulting in proliferation and proinflammatory cytokine production.
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Base de dados:
MEDLINE
Assunto principal:
Beriliose
/
Berílio
/
Linfócitos T CD4-Positivos
/
Antígenos HLA-DP
/
Fator de Necrose Tumoral alfa
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article