Regulatory T-cell recovery in recipients of haploidentical nonmyeloablative hematopoietic cell transplantation with a humanized anti-CD2 mAb, MEDI-507, with or without fludarabine.
Exp Hematol
; 35(7): 1140-52, 2007 Jul.
Article
em En
| MEDLINE
| ID: mdl-17588483
ABSTRACT
OBJECTIVE:
We have evaluated T-cell reconstitution and reactivity in patients receiving nonmyeloablative haploidentical hematopoietic cell transplantation (HCT) protocols involving an anti-CD2 monoclonal antibody (MEDI 507) to treat chemorefractory hematopoietic malignancies.METHODS:
Three cohorts of four patients each and one cohort of six patients received one of four Medi-507-based regimens, all of which included cyclophosphamide, thymic irradiation, and a short posttransplantation course of cyclosporine.RESULTS:
Following marked T-cell depletion, initially recovering CD4 and CD8 T cells were mainly memory-type cells. A high percentage of CD4 T cells expressed high levels of CD25 in recipients of all protocols, except the only protocol to include fludarabine, early post-HCT. CD25 expression varied inversely with T-cell concentrations in blood. CD25(high) CD4 T cells expressed Foxp3 and cytotoxic T-lymphocyte-associated protein 4, indicating that they were regulatory T cells (Treg).CONCLUSIONS:
Fludarabine treatment prevents Treg enrichment after haploidentical nonmyeloablative stem cell transplantation, presumably by depleting recipient Tregs. In vitro analyses of allorecognition were consistent with a cytokine-mediated rejection process in one case and in another provided proof of principle that mixed chimerism achieved without graft-vs-host disease induces donor- and recipient-specific tolerance. More reliable achievement of this outcome could provide a promising strategy for organ allograft tolerance induction.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vidarabina
/
Linfócitos T Reguladores
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Transplante de Células-Tronco Hematopoéticas
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Anticorpos Monoclonais
Tipo de estudo:
Guideline
Limite:
Humans
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article