Intrathymic transplantation of bone marrow-derived progenitors provides long-term thymopoiesis.
Blood
; 115(10): 1913-20, 2010 Mar 11.
Article
en En
| MEDLINE
| ID: mdl-20040762
ABSTRACT
The sustained differentiation of T cells in the thymus cannot be maintained by resident intrathymic (IT) precursors and requires that progenitors be replenished from the bone marrow (BM). In patients with severe combined immunodeficiency (SCID) treated by hematopoietic stem cell transplantation, late T-cell differentiation defects are thought to be due to an insufficient entry of donor BM progenitors into the thymus. Indeed, we find that the intravenous injection of BM progenitors into nonconditioned zeta-chain-associated protein kinase 70 (ZAP-70)-deficient mice with SCID supports short- but not long-term thymopoiesis. Remarkably, we now show that the IT administration of these progenitors produces a significant level of donor-derived thymopoiesis for more than 6 months after transplantation. In contrast to physiologic thymopoiesis, long-term donor thymopoiesis was not due to the continued recruitment of progenitors from the BM. Rather, IT transplantation resulted in the unique generation of a large population of early c-Kit(high) donor precursors within the thymus. These ZAP-70-deficient mice that received an IT transplant had a significantly increased prothymocyte niche compared with their untreated counterparts; this phenotype was associated with the generation of a medulla. Thus, IT administration of BM progenitors results in the filling of an expanded precursor niche and may represent a strategy for enhancing T-cell differentiation in patients with SCID.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Timo
/
Trasplante de Médula Ósea
/
Linfopoyesis
/
Células Progenitoras Linfoides
Límite:
Animals
Idioma:
En
Revista:
Blood
Año:
2010
Tipo del documento:
Article
País de afiliación:
Francia