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RESEARCH PRODUCT
Human γδ T-Cells: From Surface Receptors to the Therapy of High-Risk Leukemias
Vito PistoiaNicola TuminoPaola VaccaIrene VenezianiAlessandro MorettaFranco LocatelliFranco LocatelliLorenzo Morettasubject
lcsh:Immunologic diseases. Allergy0301 basic medicineαβ T-cellChemokineB-cell depletion; hematopoietic stem cells; HLA-haploidentical transplantation; receptors; αβ T-cell; γδ T-cellsReceptors Antigen T-Cell alpha-betaMini ReviewHLA-haploidentical transplantationImmunologyGenes MHC Class Ichemical and pharmacologic phenomenaMajor histocompatibility complexCD19Mice03 medical and health sciencesγδ T-cellsAntigenReceptorsMHC class ImedicineAnimalsHumansImmunology and AllergyIntraepithelial LymphocytesB-LymphocytesLeukemiaB-cell depletionbiologyT-cell receptorHematopoietic Stem Cell Transplantationmedicine.diseaseNKG2DKiller Cells NaturalLeukemia030104 developmental biologySettore MED/38 - PEDIATRIA GENERALE E SPECIALISTICACytomegalovirus InfectionsImmunologybiology.proteinlcsh:RC581-607Hematopoietic stem cellsdescription
γδ T lymphocytes are potent effector cells, capable of efficiently killing tumor and leukemia cells. Their activation is mediated by γδ T-cell receptor (TCR) and by activating receptors shared with NK cells (e.g., NKG2D and DNAM-1). γδ T-cell triggering occurs upon interaction with specific ligands, including phosphoantigens (for Vγ9Vδ2 TCR), MICA-B and UL16 binding protein (for NKG2D), and PVR and Nectin-2 (for DNAM-1). They also respond to cytokines undergoing proliferation and release of cytokines/chemokines. Although at the genomic level γδ T-cells have the potential of an extraordinary TCR diversification, in tissues they display a restricted repertoire. Recent studies have identified various γδ TCR rearrangements following either hematopoietic stem cell transplantation (HSCT) or cytomegalovirus infection, accounting for their “adaptive” potential. In humans, peripheral blood γδ T-cells are primarily composed of Vγ9Vδ2 chains, while a minor proportion express Vδ1. They do not recognize antigens in the context of MHC molecules, thus bypassing tumor escape based on MHC class I downregulation. In view of their potent antileukemia activity and absence of any relevant graft-versus-host disease-inducing effect, γδ T-cells may play an important role in the successful clinical outcome of patients undergoing HLA-haploidentical HSCT depleted of TCR αβ T/CD19+ B lymphocytes to cure high-risk acute leukemias. In this setting, high numbers of both γδ T-cells (Vδ1 and Vδ2) and NK cells are infused together with CD34+ HSC and may contribute to rapid control of infections and leukemia relapse. Notably, zoledronic acid potentiates the cytolytic activity of γδ T-cells in vitro and its infusion in patients strongly promotes γδ T-cell differentiation and cytolytic activity; thus, treatment with this agent may contribute to further improve the patient clinical outcome after HLA-haploidentical HSCT depleted of TCR αβ T/CD19+ B lymphocytes.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2018-01-31 | Frontiers in Immunology |