Delineation of immunoregulatory properties of adult T-cell leukemia cells

Yasushi Matsubara, Toshiyuki Hori, Rimpei Morita, Shimon Sakaguchi, Takashi Uchiyama

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

We characterized leukemic cells from 20 adult T-cell leukemia (ATL) cases and 7 ATL-derived cell lines in terms of Foxp3 messenger RNA (mRNA) expression, cytokine production, cell surface markers associated with regulatory T-cells (Treg), and in vitro immunoregulatory activity and compared the results with those of cells from 3 T-cell-type chronic lymphocytic leukemia (T-CLL) patients and normal CD4+ T-cells. Real-time polymerase chain reaction analysis showed that cells from 10 ATL cases, 1 T-CLL case, and 1 ATL cell line had higher Foxp3 mRNA levels than CD4+ T-cells. In 5 ATL cases, Foxp3 levels were comparable to those of CD4+CD25+ T-cells. Flow cytometric analysis revealed that CTLA-4 expression correlated with Foxp3 mRNA level in ATL cells. The cells of all ATL cases examined produced no interleukin 2 or interferon γ after ionomycin and phorbolmyristate acetate stimulation. Cases with low Foxp3 expression (Foxp3-low) tended to express higher levels of transforming growth factor β mRNA, but this trend was not statistically significant. An in vitro inhibition assay showed that the proliferation of normal CD4+CD25- T-cells stimulated with anti-CD3 monoclonal antibody and autologous dendritic cells was significantly suppressed by coculture with Foxp3-high ATL cells. These results indicate that Foxp3 expression is variable in ATL cases and that Foxp3-high ATL cells, which resemble Treg phenotypically as well as functionally, may be involved in immune suppression in ATL.

Original languageEnglish
Pages (from-to)63-69
Number of pages7
JournalInternational journal of hematology
Volume84
Issue number1
DOIs
Publication statusPublished - 2006 Jul 1

Keywords

  • Adult T-cell leukemia
  • CTLA-4
  • Foxp3
  • Regulatory T-cell

ASJC Scopus subject areas

  • Hematology

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