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

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.

• Authors: Giorgia Serafini, Marco Andreani, Manuela Testi, MariaRosa Battarra, Andrea Bontadini, Eika Biral, Katharina Fleischhauer, Sarah Marktel, Guido Lucarelli, Maria Grazia Roncarolo, Rosa Bacchetta
• Journal: Haematologica (Haematologica) Vol. 94 Issue 10 Pg. 1415-26 (Oct 2009) ISSN: 1592-8721 [Electronic] Italy
• PMID: 19608686 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• IL10 protein, human
• Interleukin-10

Topics

• Child
• Child, Preschool
• Chimerism
• Erythroid Cells (immunology)
• Female
• Hematopoietic Stem Cell Transplantation (adverse effects)
• Humans
• Interleukin-10 (immunology)
• Male
• T-Lymphocytes, Regulatory (immunology, transplantation)
• Thalassemia (genetics, immunology, surgery)
• Transplantation, Homologous