Abstract | BACKGROUND: 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.
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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)
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Chemical References |
- IL10 protein, human
- Interleukin-10
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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
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