Rapid reconstitution of CD4 T cells and NK cells protects against CMV-reactivation after allogeneic stem cell transplantation

J Transl Med. 2016 Aug 2;14(1):230. doi: 10.1186/s12967-016-0988-4.

Abstract

Background: Epstein-Barr virus and Cytomegalovirus reactivations frequently occur after allogeneic stem cell transplantation (SCT).

Methods: Here we investigated the role of immune cell reconstitution in the onset and subsequent severity of EBV- and CMV-reactivation. To this end, 116 patients were prospectively sampled for absolute T cell (CD4 and CD8), B-cell (CD19) and NK-cell (CD16 and CD56) numbers weekly post-SCT during the first 3 months and thereafter monthly until 6 months post-SCT. Viral load was monitored in parallel.

Results: In contrast to the general belief, we found that early T-cell reconstitution does not play a role in the onset of viral reactivation. CMV reactivation in the first 7 weeks after SCT however resulted in higher absolute CD8(+) T-cell numbers 6 months post-SCT in patients with high-level reactivation, many of which were CMV-specific. Interestingly, rapid reconstitution of CD4(+) T-cells, as well as NK cells and the presence of donor KIR3DL1, are associated with the absence of CMV-reactivation after SCT, suggestive of a protective role of these cells. In contrast, EBV-reactivations were not affected in any way by the level of immune reconstitution after SCT.

Conclusion: In conclusion, these data suggest that CD4(+) T-cells and NK cells, rather than CD8(+) T-cells, are associated with protection against CMV-reactivation.

Keywords: CMV; EBV; Immune reconstitution; Stem cell transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cytomegalovirus / immunology*
  • Cytoprotection*
  • Female
  • Humans
  • Killer Cells, Natural / immunology*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Receptors, KIR3DL1 / metabolism
  • Risk Factors
  • Stem Cell Transplantation*
  • Transplantation, Homologous
  • Young Adult

Substances

  • KIR3DL1 protein, human
  • Receptors, KIR3DL1