Abstract
BackgroundEpstein-Barr virus and Cytomegalovirus reactivations frequently occur after allogeneic stem cell transplantation (SCT).MethodsHere 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.ResultsIn 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.ConclusionIn conclusion, these data suggest that CD4+ T-cells and NK cells, rather than CD8+ T-cells, are associated with protection against CMV-reactivation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0988-4) contains supplementary material, which is available to authorized users.
Highlights
Epstein-Barr virus and Cytomegalovirus reactivations frequently occur after allogeneic stem cell transplantation (SCT)
We show that presence of donor inhibitory killer cell immunoglobulin-like receptor (KIR) KIR3DL1, rapid reconstitution of CD4+ T-cells and Natural Killer (NK) cells early after SCT is protective against CMV reactivation
Transplantation associated risk factors that could influence the onset of viral reactivation were assessed in univariate analysis (Table 1)
Summary
Epstein-Barr virus and Cytomegalovirus reactivations frequently occur after allogeneic stem cell transplantation (SCT). Herpesvirus reactivations, both Epstein-Barr virus (EBV) [1] and Cytomegalovirus (CMV) [2, 3], occur frequently after allogeneic hematopoietic stem cell transplantation (SCT) Both viruses persist lifelong in the host in whom there is a tightly regulated balance between the virus infected cells and control by cytotoxic T-cell responses [1, 4, 5]. Frequent monitoring of EBV and CMV-DNA loads post transplantation is used to detect viral reactivations and infections providing a basis for pre-emptive therapy to prevent clinical complications [7, 8] Both CD8+ T-cells as well as Natural Killer (NK) cells are key effector cells in eliminating virus-infected cells [9, 10]. For CMV, recovery of CMV-specific T-cells to levels greater than
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