The Role of γδ T Cells as a Line of Defense in Viral Infections after Allogeneic Stem Cell Transplantation: Opportunities and Challenges |
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Authors: | Anke Janssen Eline van Diest Anna Vyborova Lenneke Schrier Anke Bruns Zsolt Sebestyen Trudy Straetemans Moniek de Witte Jürgen Kuball |
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Institution: | 1.Department of Hematology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; (A.J.); (T.S.); (M.d.W.);2.Center for Translational Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; (E.v.D.); (A.V.); (L.S.); (Z.S.);3.Princess Maxima Center for Pediatric Oncology, 3584 CX Utrecht, The Netherlands;4.Department of Infectious Diseases, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; |
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Abstract: | In the complex interplay between inflammation and graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (allo-HSCT), viral reactivations are often observed and cause substantial morbidity and mortality. As toxicity after allo-HSCT within the context of viral reactivations is mainly driven by αβ T cells, we describe that by delaying αβ T cell reconstitution through defined transplantation techniques, we can harvest the full potential of early reconstituting γδ T cells to control viral reactivations. We summarize evidence of how the γδ T cell repertoire is shaped by CMV and EBV reactivations after allo-HSCT, and their potential role in controlling the most important, but not all, viral reactivations. As most γδ T cells recognize their targets in an MHC-independent manner, γδ T cells not only have the potential to control viral reactivations but also to impact the underlying hematological malignancies. We also highlight the recently re-discovered ability to recognize classical HLA-molecules through a γδ T cell receptor, which also surprisingly do not associate with GVHD. Finally, we discuss the therapeutic potential of γδ T cells and their receptors within and outside the context of allo-HSCT, as well as the opportunities and challenges for developers and for payers. |
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Keywords: | γ δ T cells allogeneic stem cell transplantation viral infections CMV EBV T cell depletion |
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