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γδT cells elicited by CMV reactivation after allo-SCT cross-recognize CMV and leukemia.

Authors
  • Scheper, W
  • van Dorp, S
  • Kersting, S
  • Pietersma, F
  • Lindemans, C
  • Hol, S
  • Heijhuurs, S
  • Sebestyen, Z
  • Gründer, C
  • Marcu-Malina, V
  • Marchant, A
  • Donner, C
  • Plachter, B
  • Vermijlen, D
  • van Baarle, D
  • Kuball, J
Type
Published Article
Journal
Leukemia
Publisher
Springer Nature
Publication Date
Jun 01, 2013
Volume
27
Issue
6
Pages
1328–1338
Identifiers
DOI: 10.1038/leu.2012.374
PMID: 23277330
Source
Medline
License
Unknown

Abstract

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 Vδ2-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. Vδ2(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 and primary leukemic blasts. CMV and leukemia reactivity were restricted to the same clonal population, whereas other Vδ2(neg) T cells interact with dendritic cells (DCs). Cloned Vδ1 T-cell receptors (TCRs) mediated leukemia reactivity and DC interactions, but surprisingly not CMV reactivity. Interestingly, CD8αα expression appeared to be a signature of γδT cells after CMV exposure. However, functionally, CD8αα was primarily important in combination with selected leukemia-reactive Vδ1 TCRs, demonstrating for the first time a co-stimulatory role of CD8αα for distinct γδTCRs. Based on these observations, we advocate the exploration of adoptive transfer of unmodified Vδ2(neg) γδT cells after allo-SCT to tackle CMV reactivation and residual leukemic blasts, as well as application of leukemia-reactive Vδ1 TCR-engineered T cells as alternative therapeutic tools.

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