Type 1 regulatory T cells are associated with persistent split erythroid/lymphoid chimerism after allogeneic hematopoietic stem cell transplantation for thalassemia

Giorgia Serafini, Marco Andreani, Manuela Testi, MariaRosa Battarra, Andrea Bontadini, Eika Biral, Katharina Fleischhauer, Sarah Marktel, Guido Lucarelli, Maria Grazia Roncarolo, Rosa Bacchetta

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Thalassemia major can be cured with allogeneic hematopoietic stem cell transplantation. Persistent mixed chimerism develops in around 10% of transplanted thalassemic patients, but the biological mechanisms underlying this phenomenon are poorly understood. Design and Methods: The presence of interleukin-10-producing T cells in the peripheral blood of eight patients with persistent mixed chimerism and five with full donor chimerism was investigated. A detailed characterization was then performed, by T-cell cloning, of the effector and regulatory T-cell repertoire of one patient with persistent mixed chimerism, who developed stable split erythroid/lymphoid chimerism after a hematopoietic stem cell transplant from an HLA-matched unrelated donor. Results: Higher levels of interleukin-10 were produced by peripheral blood mononuclear cells from patients with persistent mixed chimerism than by the same cells from patients with complete donor chimerism or normal donors. T-cell clones of both host and donor origin could be isolated from the peripheral blood of one, selected patient with persistent mixed chimerism. Together with effector T-cell clones reactive against host or donor alloantigens, regulatory T-cell clones with a cytokine secretion profile typical of type 1 regulatory cells were identified at high frequencies. Type 1 regulatory cell clones, of both donor and host origin, were able to inhibit the function of effector T cells of either donor or host origin in vitro. Conclusions: Overall these results suggest that interleukin-10 and type 1 regulatory cells are associated with persistent mixed chimerism and may play an important role in sustaining long-term tolerance in vivo. These data provide new insights into the mechanisms of peripheral tolerance in chimeric patients and support the use of cellular therapy with regulatory T cells following hematopoietic stem cell transplantation.

Original languageEnglish
Pages (from-to)1415-1426
Number of pages12
JournalHaematologica
Volume94
Issue number10
DOIs
Publication statusPublished - Oct 2009

Keywords

  • Hematopoietic stem cell transplantation
  • Persistent mixed chimerism
  • Thalassemia
  • Tolerance
  • Type 1 regulatory T (Tr1) cells

ASJC Scopus subject areas

  • Hematology

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