The role of Vδ2-negative γδ T cells during cytomegalovirus reactivation in recipients of allogeneic stem cell transplantation

Andrea Knight, Alejandro J Madrigal, Sarah Grace, Janani Sivakumaran, Panagiotis Kottaridis, Stephen Mackinnon, Paul J Travers, Mark W Lowdell

Research output: Contribution to journalArticlepeer-review

Abstract

Reactivation of cytomegalovirus (CMV) remains a serious complication after allogeneic stem cell transplantation, but the role of γδ T cells is undefined. We have studied the immune reconstitution of Vδ2negative (Vδ2neg) γδ T cells, including Vδ1 and Vδ3 subsets and Vδ2positive (Vδ2pos) γδ T cells in 40 patients during the first 24 months after stem cell transplantation. Significant long-term expansions of Vδ2neg but not Vδ2pos γδ T cells were observed during CMV reactivation early after transplantation, suggesting direct involvement of γδ T cells in anti-CMV immune responses. Similarly, significantly higher numbers of Vδ2neg γδ T cells were detected in CMV-seropositive healthy persons compared with seronegative donors; the absolute numbers of Vδ2pos cells were not significantly different. The expansion of Vδ2neg γδ T cells appeared to be CMV-related because it was absent in CMV-negative/Epstein-Barr virus-positive patients. T-cell receptor-δ chain determining region 3 spectratyping of Vδ2neg γδ T cells in healthy subjects and patients showed restricted clonality. Polyclonal Vδ2neg cell lines generated from CMV-seropositive healthy donors and from a recipient of a graft from a CMV-positive donor lysed CMV-infected targets in all cases. Our study shows new evidence for role of γδ T cells in the immune response to CMV reactivation in transplantation recipients.
Original languageEnglish
Pages (from-to)2164-2172
Number of pages9
JournalBlood
Volume116
Issue number12
DOIs
Publication statusPublished - 23 Sep 2010

Keywords

  • Young Adult
  • Humans
  • Child
  • Transplantation, Homologous
  • Virus Activation
  • Cell Proliferation
  • Cytomegalovirus
  • Adult
  • Hematopoietic Stem Cell Transplantation
  • Cytomegalovirus Infections
  • Receptors, Antigen, T-Cell, gamma-delta
  • Middle Aged
  • Adolescent
  • Female
  • Male
  • T-Lymphocyte Subsets

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