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

Jing Chen, Mike Petrus, Bonita R. Bryant, Vinh Phuc Nguyen, Mindy Stamer, Carolyn K. Goldman, Richard Bamford, John C. Morris, John Edward Janik, Thomas A. Waldmann

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43 Scopus citations

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-κB motif in its proximal promoter, whereas IL-9 receptor-α (IL-9Rα) expression is not induced by Tax. However, supporting a role for IL-9/IL-9Rα in ATL, a neutralizing monoclonal antibody directed toward IL-9Rα 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-9Rα 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-9Rα/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.

Original languageEnglish (US)
Pages (from-to)5163-5172
Number of pages10
JournalBlood
Volume111
Issue number10
DOIs
StatePublished - May 15 2008

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Chen, J., Petrus, M., Bryant, B. R., Nguyen, V. P., Stamer, M., Goldman, C. K., Bamford, R., Morris, J. C., Janik, J. E., & Waldmann, T. A. (2008). Induction of the IL-9 gene by HTLV-I Tax stimulates the spontaneous proliferation of primary adult T-eell leukemia cells by a paracrine mechanism. Blood, 111(10), 5163-5172. https://doi.org/10.1182/blood-2007-09-113654