Chronic overexpression of membrane-bound flt3 ligand by T lymphocytes in severe aplastic anaemia

Otmar Pfister, Elena Chklovskaia, Wendy Jansen, Kinga Meszáros, Catherine Nissen, Christoph Rahner, Nina Hurwitz, Natalia Bogatcheva, Stewart D. Lyman, Aleksandra Wodnar-Filipowicz

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Aplastic anaemia (AA) is an immune-mediated bone marrow failure associated with high serum levels of flt3 ligand (FL). We examined expression of the membrane-bound isoform of FL in peripheral blood and bone marrow cells from AA patients at diagnosis (n = 16) and after immunosuppressive (IS) treatment (n = 36). Flow cytometry demonstrated strongly increased FL levels on the cell surface of T lymphocytes in AA relative to normal controls (P < 0.0001). T-cell-specific expression of membrane-bound FL was confirmed by confocal microscopy. FL mRNA and total cellular FL protein levels were increased about threefold. Overexpression of FL in AA was observed for up to 20 years after IS treatment. FL levels correlated inversely with CD34+ cell numbers and the colony-forming ability of AA bone marrow (R = -0.68 and -0.85 respectively). Histological examination of spleen specimens and bone marrow biopsies gave no evidence of degeneration or fibrosis due to prolonged exposure to high FL. Levels of membrane-bound FL were not increased in autoimmune diseases (n = 23), including rheumatoid arthritis and lupus erythematosus, nor in graft-versus-host disease (n = 8). Chronic overexpression of FL on the surface of T lymphocytes in AA, but not in other T-cell-mediated disorders, suggests that membrane-bound FL plays a role in cell-cell interactions in bone marrow failure and may be important for long- term haemopoietic recovery.

Original languageEnglish (US)
Pages (from-to)211-220
Number of pages10
JournalBritish journal of haematology
Volume109
Issue number1
DOIs
StatePublished - Jun 20 2000
Externally publishedYes

Keywords

  • Aplastic anaemia
  • Bone marrow and spleen fibrosis
  • Flt3 ligand
  • Membrane-bound cytokines
  • T lymphocytes

ASJC Scopus subject areas

  • Hematology

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    Pfister, O., Chklovskaia, E., Jansen, W., Meszáros, K., Nissen, C., Rahner, C., Hurwitz, N., Bogatcheva, N., Lyman, S. D., & Wodnar-Filipowicz, A. (2000). Chronic overexpression of membrane-bound flt3 ligand by T lymphocytes in severe aplastic anaemia. British journal of haematology, 109(1), 211-220. https://doi.org/10.1046/j.1365-2141.2000.02008.x