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Type 1 regulatory T cells are associated with persistent split erythroid/lymphoid chimerism after allogeneic hematopoietic stem cell transplantation for thalassemia.
- Source :
-
Haematologica [Haematologica] 2009 Oct; Vol. 94 (10), pp. 1415-26. Date of Electronic Publication: 2009 Jul 16. - Publication Year :
- 2009
-
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.<br />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.<br />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.<br />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.
- Subjects :
- Child
Child, Preschool
Female
Humans
Interleukin-10 immunology
Male
T-Lymphocytes, Regulatory immunology
Thalassemia genetics
Thalassemia immunology
Transplantation, Homologous
Chimerism
Erythroid Cells immunology
Hematopoietic Stem Cell Transplantation adverse effects
T-Lymphocytes, Regulatory transplantation
Thalassemia surgery
Subjects
Details
- Language :
- English
- ISSN :
- 1592-8721
- Volume :
- 94
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Haematologica
- Publication Type :
- Academic Journal
- Accession number :
- 19608686
- Full Text :
- https://doi.org/10.3324/haematol.2008.003129