Human γδ T-Cells: From Surface Receptors to the Therapy of High-Risk Leukemias
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,...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00984/full |
| _version_ | 1819133369185730560 |
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| author | Vito Pistoia Nicola Tumino Paola Vacca Irene Veneziani Alessandro Moretta Franco Locatelli Franco Locatelli Lorenzo Moretta |
| author_facet | Vito Pistoia Nicola Tumino Paola Vacca Irene Veneziani Alessandro Moretta Franco Locatelli Franco Locatelli Lorenzo Moretta |
| author_sort | Vito Pistoia |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T09:46:12Z |
| format | Article |
| id | doaj.art-ff8da52d5cbc4a7d9b30ddddff321793 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-22T09:46:12Z |
| publishDate | 2018-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-ff8da52d5cbc4a7d9b30ddddff3217932022-12-21T18:30:32ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-05-01910.3389/fimmu.2018.00984358354Human γδ T-Cells: From Surface Receptors to the Therapy of High-Risk LeukemiasVito Pistoia0Nicola Tumino1Paola Vacca2Irene Veneziani3Alessandro Moretta4Franco Locatelli5Franco Locatelli6Lorenzo Moretta7Immunology Area, IRCCS Bambino Gesù Pediatric Hospital, Rome, ItalyImmunology Area, IRCCS Bambino Gesù Pediatric Hospital, Rome, ItalyImmunology Area, IRCCS Bambino Gesù Pediatric Hospital, Rome, ItalyImmunology Area, IRCCS Bambino Gesù Pediatric Hospital, Rome, ItalyDipartimento di Medicina Sperimentale and Centro di Eccellenza per le Ricerche Biomediche, Università degli Studi di Genova, Genoa, ItalyDepartment of Onco-Hematology and Cell and Gene Therapy, IRCCS Bambino Gesù Pediatric Hospital, Rome, ItalyDepartment of Pediatric Science, University of Pavia, Pavia, ItalyImmunology Area, IRCCS Bambino Gesù Pediatric Hospital, Rome, Italyγδ 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.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00984/fullγδ T-cellsreceptorshematopoietic stem cellsHLA-haploidentical transplantationαβ T-cellB-cell depletion |
| spellingShingle | Vito Pistoia Nicola Tumino Paola Vacca Irene Veneziani Alessandro Moretta Franco Locatelli Franco Locatelli Lorenzo Moretta Human γδ T-Cells: From Surface Receptors to the Therapy of High-Risk Leukemias Frontiers in Immunology γδ T-cells receptors hematopoietic stem cells HLA-haploidentical transplantation αβ T-cell B-cell depletion |
| title | Human γδ T-Cells: From Surface Receptors to the Therapy of High-Risk Leukemias |
| title_full | Human γδ T-Cells: From Surface Receptors to the Therapy of High-Risk Leukemias |
| title_fullStr | Human γδ T-Cells: From Surface Receptors to the Therapy of High-Risk Leukemias |
| title_full_unstemmed | Human γδ T-Cells: From Surface Receptors to the Therapy of High-Risk Leukemias |
| title_short | Human γδ T-Cells: From Surface Receptors to the Therapy of High-Risk Leukemias |
| title_sort | human γδ t cells from surface receptors to the therapy of high risk leukemias |
| topic | γδ T-cells receptors hematopoietic stem cells HLA-haploidentical transplantation αβ T-cell B-cell depletion |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00984/full |
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