Impaired NK cell differentiation of blood-derived CD34+ progenitors from patients with myeloid metaplasia with myelofibrosis

Diane Briard, Danièle Brouty-Boyé, Julien Giron-Michel, Bruno Azzarone, Claude Jasmin, Caroline Le Bousse-Kerdilès

Research output: Contribution to journalArticlepeer-review

Abstract

Cultured blood CD34+ progenitors from patients with myeloid metaplasia with myelofibrosis (MMM) failed to differentiate into natural killer (NK) cells with recombinant interleukin (IL)-15. No NK cells either could be induced in coculture with IL-15-expressing fibroblasts from MMM patients' spleens. The impaired NK differentiation could be circumvented by using normal blood CD34+ cells in the coculture. In this case, cell-to-cell contact and IL-15 interaction were crucial for NK cell differentiation. Pretreatment of normal CD34+ progenitors with anti-IL-15 monoclonal antibody markedly reduced NK cell production while MMM fibroblast pretreatment did not. Both normal and MMM progenitors constitutively expressed IL-15. Analysis of endogenous IL-15 signaling pathway revealed a constitutive γc/Jak3 association and STAT3 activation in the two types of progenitors. Anti-IL-15 monoclonal antibody treatment caused a downregulation of IL-15 signaling in normal but not MMM blood cells. The impaired NK differentiation in MMM may thus arise from a deregulated control of an endogenous IL-15 involved in hematopoietic progenitors' lymphoid differentiation.

Original languageEnglish
Pages (from-to)201-212
Number of pages12
JournalClinical Immunology
Volume106
Issue number3
DOIs
Publication statusPublished - Mar 1 2003

Keywords

  • Blood CD34 cells
  • Fibroblast
  • IL-15
  • Myeloid metaplasia with myelofibrosis
  • NK cell differentiation
  • Signaling pathway

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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