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Blood. 2008 May 15;111(10):5163-72. doi: 10.1182/blood-2007-09-113654. Epub 2008 Mar 13.

Induction of the IL-9 gene by HTLV-I Tax stimulates the spontaneous proliferation of primary adult T-cell leukemia cells by a paracrine mechanism.

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1
Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.

Abstract

The etiologic agent of adult T-cell leukemia (ATL) is human T cell lymphotropic virus type I (HTLV-I). The HTLV-I protein Tax alters gene expression, including those of cytokines and their receptors, which plays an important role in early stages of ATL. Here we demonstrate that expression of interleukin-9 (IL-9) is activated by Tax via an NF-kappaB motif in its proximal promoter, whereas IL-9 receptor-alpha (IL-9Ralpha) expression is not induced by Tax. However, supporting a role for IL-9/IL-9Ralpha in ATL, a neutralizing monoclonal antibody directed toward IL-9Ralpha inhibited ex vivo spontaneous proliferation of primary ATL cells from several patients. Fluorescence-activated cell sorter analysis of freshly isolated peripheral blood mononuclear cells from these patients revealed high level expression of IL-9Ralpha on their CD14-expressing monocytes. Furthermore, purified T cells or monocytes alone from these patients did not proliferate ex vivo, whereas mixtures of these cell types manifested significant proliferation through a contact-dependent manner. Taken together, our data suggest that primary ATL cells, via IL-9, support the action of IL-9Ralpha/CD14-expressing monocytes, which subsequently support the ex vivo spontaneous proliferation of malignant T cells. In summary, these data support a role for IL-9 and its receptor in ATL by a paracrine mechanism.

PMID:
18339896
PMCID:
PMC2384140
DOI:
10.1182/blood-2007-09-113654
[Indexed for MEDLINE]
Free PMC Article
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