| γδT-cells elicited by CMV-reactivation after allo-SCT cross-recognize CMV and leukemia. | |
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MedLine Citation:
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PMID: 23277330 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Human cytomegalovirus (CMV) infections and relapse of disease remain major problems after allogeneic stem cell transplantation (allo-SCT), in particular in combination with CMV-negative donors or cordblood transplantations. Recent data suggest a paradoxical association between CMV-reactivation after allo-SCT and reduced leukemic relapse. Given the potential of Vä2-negative γδT-cells to recognize CMV-infected cells and tumor cells, the molecular biology of distinct γδT-cell-subsets expanding during CMV-reactivation after allo-SCT was investigated. Vä2(neg) γδT-cell expansions after CMV-reactivation were observed not only with conventional but also cordblood donors. Expanded γδT-cells were capable of recognizing both CMV-infected cells as well as primary leukemic blasts. CMV- and leukemia-reactivity were restricted to the same clonal population, whereas other Vä2(neg) T-cells interact with dendritic cells (DCs). Cloned Vä1-TCRs mediated leukemia-reactivity and DC-interactions, but surprisingly not CMV-reactivity. Interestingly, CD8áá expression appeared to be a signature of γδT-cells after CMV exposure. However, functionally CD8áá was primarily important in combination with selected leukemia-reactive Vä1-TCRs, demonstrating for the first time a co-stimulatory role of CD8áá for distinct γδTCRs. Based on these observations, we advocate the exploration of adoptive transfer of unmodified Vä2(neg) γδT-cells after allo-SCT to tackle CMV-reactivation and residual leukemic blasts, as well as application of leukemia-reactive Vä1-TCR-engineered T-cells as alternative therapeutic tools.Leukemia accepted article preview online, 1 January 2013; doi:10.1038/leu.2012.374. |
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Authors:
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W Scheper; S van Dorp; S Kersting; F Pietersma; C Lindemans; S Hol; S Heijhuurs; Z Sebestyen; C Gründer; V Marcu-Malina; A Marchant; C Donner; B Plachter; D Vermijlen; D van Baarle; J Kuball |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-1-01 |
Journal Detail:
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Title: Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K Volume: - ISSN: 1476-5551 ISO Abbreviation: Leukemia Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-1 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8704895 Medline TA: Leukemia Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Hematology and Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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