γδ T-cell reconstitution after HLA-haploidentical hematopoietic transplantation depleted of TCR-αß+/CD19+ lymphocytes.
Blood
; 125(15): 2349-58, 2015 Apr 09.
Article
in En
| MEDLINE
| ID: mdl-25612623
ABSTRACT
We prospectively assessed functional and phenotypic characteristics of γδ T lymphocytes up to 7 months after HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) depleted of αß(+) T cells and CD19(+) B cells in 27 children with either malignant or nonmalignant disorders. We demonstrate that (1) γδ T cells are the predominant T-cell population in patients during the first weeks after transplantation, being mainly, albeit not only, derived from cells infused with the graft and expanding in vivo; (2) central-memory cells predominated very early posttransplantation for both Vδ1 and Vδ2 subsets; (3) Vδ1 cells are specifically expanded in patients experiencing cytomegalovirus reactivation and are more cytotoxic compared with those of children who did not experience reactivation; (4) these subsets display a cytotoxic phenotype and degranulate when challenged with primary acute myeloid and lymphoid leukemia blasts; and (5) Vδ2 cells are expanded in vitro after exposure to zoledronic acid (ZOL) and efficiently lyse primary lymphoid and myeloid blasts. This is the first detailed characterization of γδ T cells emerging in peripheral blood of children after CD19(+) B-cell and αß(+) T-cell-depleted haplo-HSCT. Our results can be instrumental to the development of clinical trials using ZOL for improving γδ T-cell killing capacity against leukemia cells. This trial was registered at www.clinicaltrials.gov as #NCT01810120.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
B-Lymphocytes
/
T-Lymphocytes
/
Leukemia
/
Receptors, Antigen, T-Cell, gamma-delta
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Receptors, Antigen, T-Cell, alpha-beta
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Hematopoietic Stem Cell Transplantation
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Antigens, CD19
Limits:
Adolescent
/
Child
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Child, preschool
/
Female
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Humans
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Infant
/
Male
Language:
En
Journal:
Blood
Year:
2015
Document type:
Article