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γδT-cells elicited by CMV-reactivation after allo-SCT cross-recognize CMV and leukemia.
MedLine Citation:
PMID:  23277330     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  JOURNAL ARTICLE     Date:  2013-1-01
Journal Detail:
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:
Created Date:  2013-1-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8704895     Medline TA:  Leukemia     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Hematology and Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
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