Generation of leukemia-specific T-helper type 1 cells applicable to human leukemia cell-therapy

Taku Fujimura, Kenji Chamoto, Takemasa Tsuji, Takeshi Sato, Hiroshi Yokouchi, Setsuya Aiba, Hachiro Tagami, Junji Tanaka, Masahiro Imamura, Yuji Togashi, Toshiaki Koda, Takashi Nishimura

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Leukemic dendritic cells (DC) were induced from the peripheral blood (PB) or bone marrow (BM) of leukemia patients by culture with (i) GM-CSF + IL-3 (neutral condition); (ii) GM-CSF + IL-3 + IL-12 + IFN-γ (type 1-condition); or (iii) GM-CSF + IL-3 + IL-4 (type 2-condition). Although leukemic cells rapidly differentiated into adhesive leukemic DC in all culture conditions, type1-conditions were the most suitable for inducing leukemic DC expressing high levels of HLA and costimulatory molecules. Addition of IL-2 after 2 days of culture induced a preferential growth of minor T cell populations interacting with leukemic DC. In particular, IFN-γ-producing CD4+ Th1 cells were efficiently expanded in type 1 culture conditions but nor in neutral or type 2-conditions. However, CD4+ T cells expanded in neutral conditions showed Th1-like functions if they were pulsed with IFN-γ for 2 days before harvest. Such Th1 cells produced IFN-γ and exhibited cytotoxicity in response to autologous leukemia cells. We further demonstrated that IFN-γ production of leukemia-specific Th1 cells was blocked by anti-HLA-DR mAb. Thus, we established a novel culture system for inducing leukemia-specific Th1 cells.

Original languageEnglish
Pages (from-to)17-25
Number of pages9
JournalImmunology Letters
Volume93
Issue number1
DOIs
Publication statusPublished - 2004 Apr 30

Keywords

  • Cell-therapy
  • Leukemia
  • Leukemic DC
  • Th1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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