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γδ T cell reconstitution after HLA-haploidentical hematopoietic transplantation depleted of TCR-αβ+/CD19+ lymphocytes

Irma Airoldi, Alice Bertaina, Ignazia Prigione, Alessia Zorzoli, Daria Pagliara, Claudia Cocco, Raffaella Meazza, Fabrizio Loiacono, Barbarella Lucarelli, Maria Ester Bernardo, Giulia Barbarito, Daniela Pende, Alessandro Moretta, Vito Pistoia, Lorenzo Moretta and Franco Locatelli
This article has an Erratum 127(12):1620

Key points

  • Vδ1 and Vδ2 T cells promptly reconstitute in children given haploidentical stem cell transplantation depleted of αβ+ T and CD19+ B cells.

  • Vδ1 cells are expanded in patients experiencing CMV reactivation; zoledronic acid potentiates Vδ2 killing against leukemia blasts.

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 αβ+ T cells and CD19+ B cells in 27 children with either malignant or non-malignant disorders. We demonstrate that: i) 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, ii) central-memory cells predominated very early post-transplantation for both Vδ1 and Vδ2 subsets; iii) Vδ1 cells are specifically expanded in patients experiencing cytomegalovirus reactivation and are more cytotoxic compared to those of children who did not experience reactivation; iv) these subsets display a cytotoxic phenotype and degranulate when challenged with primary acute myeloid and lymphoid leukemia blasts; v) Vδ2 cells are expanded in vitro after exposure to zoledronic acid 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- and αβ+ T-cell depleted haplo-HSCT. Our results can be instrumental to the development of clinical trials using zoledronic acid for improving γδ T-cell killing capacity against leukemia cells.

  • Submitted September 4, 2014.
  • Accepted January 10, 2015.