Regulatory T cell-like activity of Foxp3+ adult T cell leukemia cells

Shuming Chen, Naoto Ishii, Shouji Ine, Syuichi Ikeda, Taku Fujimura, Lishomwa C. Ndhlovu, Pejman Soroosh, Kohtaro Tada, Hideo Harigae, Junichi Kameoka, Noriyuki Kasai, Takeshi Sasaki, Kazuo Sugamura

Research output: Contribution to journalArticlepeer-review

80 Citations (Scopus)

Abstract

Adult T cell leukemia (ATL) is an aggressive neoplastic disease, in which a quarter of the patients develop opportunistic infections due to cellular immunodeficiency. However, the underlying mechanism responsible for the immunosuppression has remained unclear. Recent studies have demonstrated that the leukemia cells from a subset of patients with ATL express Foxp3, a specific marker for CD25+CD4+ regulatory T (Treg) cells, which regulate the immune response by suppressing CD4+ T cell functions. However, whether there is a functional resemblance between ATL cells that have Foxp3 expression and Treg cells is still unknown. In this report, we confirmed the high expression of Foxp3 in leukemia cells from 5 of 12 ATL patients and demonstrated that ATL cells from 3 patients suppressed the proliferation of CD4+ T cells. Similarly, one of six HTLV-I-infected cell lines showed both high Foxp3 expression and suppressive activity. Like Treg cells, the suppression induced by the ATL cells from two patients and the HTLV-infected cell line appeared to be mediated by a cell-cell contact-dependent mechanism. Nevertheless, among the ATL cells that strongly expressed Foxp3, those from two of the five patients showed no apparent suppressive activity. Furthermore, retroviral transfection of Foxp3 did not confer any suppressive function on low Foxp3-expressing HTLV-I-infected cell lines. These results indicate that Foxp3 may be essential but is not sufficient for the Treg-cell-like suppressive activity of ATL cells and HTLV-I-infected cell lines.

Original languageEnglish
Pages (from-to)269-277
Number of pages9
JournalInternational immunology
Volume18
Issue number2
DOIs
Publication statusPublished - 2006 Feb

Keywords

  • ATL
  • Foxp3
  • HTLV-1
  • Regulatory T cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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