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

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

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

162 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)1328-1338
Aantal pagina's11
TijdschriftLeukemia
Volume27
Nummer van het tijdschrift6
DOI's
StatusGepubliceerd - jun. 2013
Extern gepubliceerdJa

Vingerafdruk

Duik in de onderzoeksthema's van 'γδT cells elicited by CMV reactivation after allo-SCT cross-recognize CMV and leukemia'. Samen vormen ze een unieke vingerafdruk.

Citeer dit