Inverse correlation of Vδ2+ T-cell recovery with EBV reactivation after haematopoietic stem cell transplantation

Br J Haematol. 2018 Jan;180(2):276-285. doi: 10.1111/bjh.15037. Epub 2017 Dec 21.

Abstract

Epstein-Barr virus (EBV) reactivation remains a life-threatening complication in recipients of a haploidentical haematopoietic stem cell transplantation (haploHSCT). Reconstitution of adaptive T lymphocytes is generally compromised at the early stages following transplant, suggesting an important role of other effector cells in preventing EBV infection. Our previous studies demonstrated that recovery of CD4- CD8- T cells negatively correlated with EBV reactivation after haploHSCT. In this prospective study on 132 adult patients with haematopoietic malignancy, recovery of T-cell subpopulations was characterized post-haploHSCT. We showed that the median counts of peripheral Vδ2 cells were continuously lower in recipients with EBV reactivation compared with controls at 30, 60 and 90 days after haploHSCT (P values: 0·006, <0·001 and 0·019, respectively). Landmark study further indicated that the cumulative incidence of EBV reactivation was significantly decreased in recipients with higher day-30 Vδ2 counts. Activation of Vδ2 cells upon EBV reactivation was accompanied by an induction of cell apoptosis. Cytotoxic effect of Vδ2 cells on EBV-infected cells was confirmed by in vitro experiments. Together, our findings uncovered a significant correlation of recovered Vδ2 with EBV reactivation following haploHSCT. These results will help to better understand the intrinsic anti-virus immunity and develop γδ T-based therapy strategies after haematopoietic transplantation.

Keywords: Epstein-Barr virus (EBV); Vδ2 cells; haematopoietic stem cell transplantation; immune reconstitution; γδ T.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Apoptosis / genetics
  • Apoptosis / immunology
  • Cytotoxicity, Immunologic
  • Epstein-Barr Virus Infections / diagnosis
  • Epstein-Barr Virus Infections / etiology*
  • Female
  • Genes, T-Cell Receptor delta*
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / prevention & control
  • HLA Antigens / genetics
  • HLA Antigens / immunology
  • Haplotypes
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Herpesvirus 4, Human / physiology*
  • Humans
  • Incidence
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Transplantation, Homologous
  • Virus Activation*
  • Young Adult

Substances

  • HLA Antigens