T-cell suppression mediated by mesenchymal stem cells is deficient in patients with severe aplastic anemia

Andrea Bacigalupo, Marisa Valle, Marina Podestà, Anna Pitto, Elena Zocchi, Antonio De Flora, Sara Pozzi, Silvia Luchetti, Francesco Frassoni, Maria Teresa Van Lint, Giovanna Piaggio

Research output: Contribution to journalArticlepeer-review


Objective. To compare the suppressive effect of mesenchymal stem cells (MSC), derived from normal individuals or severe aplastic anemia patients (SAA), on T-cell activation. Patients and Methods. We studied bone marrow MSC from 19 healthy donors and 23 SAA patients in different phases of the disease: at diagnosis (n = 3), following immunosuppressive therapy (IS) (n = 16), or after a bone marrow transplant (BMT) (n = 4). MSC were tested for T-cell suppression in the following assays: mixed lymphocyte reaction (MLR), phytohemaglutinin (PHA)-primed cultures, activation surface markers, γ-IFN production, hematopoietic colony formation (CFC), production of cyclic ADP-ribose (cADPR). Results. The abnormalities of SAA MSC included: 1) significantly lower suppression of T-cell proliferation induced by alloantigens (p = 0.009) or PHA (p = 0.006); 2) impaired capacity to suppress CD38 expression on PHA-primed T cells (p = 0.001); 3) impaired ability to suppress γ-IFN production in PHA cultures, resulting in an 11-fold higher γ-IFN concentration; 4) no preventive effect on T cell-mediated inhibition of CFC; and 5) significantly reduced (p = 0.009) production of cADPR, a universal calcium mobilizer. MSC-mediated suppression of PHA-induced T-cell proliferation was restored to control levels in 3 of 4 patients post-BMT. Conclusion. The ability of MSC to downregulate T-cell priming, proliferation, and cytokine release is deficient in patients with SAA, persists indefinitely after immunosuppressive therapy, but seems to be restored after BMT. Whether these abnormalities are relevant to the pathogenesis of aplastic anemia remains to be determined.

Original languageEnglish
Pages (from-to)819-827
Number of pages9
JournalExperimental Hematology
Issue number7
Publication statusPublished - Jul 2005

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation


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