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


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.
Serafini
Giorgia
G
Mediterranean Institute of Hematology, IME Foundation, Policlinico di Tor Vergata, Rome, Italy.
Andreani
Marco
M
Testi
Manuela
M
Battarra
MariaRosa
M
Bontadini
Andrea
A
Biral
Eika
E
Fleischhauer
Katharina
K
Marktel
Sarah
S
Lucarelli
Guido
G
Roncarolo
Maria Grazia
MG
Bacchetta
Rosa
R
D002648:Child; D002675:Child, Preschool; D046528:Chimerism; D041905:Erythroid Cells / Q000276:immunology; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D008297:Male; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000637:transplantation*; D013789:Thalassemia / Q000235:genetics / Q000276:immunology / Q000601:surgery*; D014184:Transplantation, Homologous
C508609:IL10 protein, human; D016753:Interleukin-10