Human herpesvirus 6 infection inhibits specific lymphocyte proliferation responses and is related to lymphocytopenia after allogeneic stem cell transplantation

Abstract

Summary:Human herpesvirus 6 (HHV-6) infection and the HHV-6-specific lymphocyte proliferation response were studied longitudinally in 24 patients in the first 3 months after allogeneic stem cell transplantation (allo-SCT). HHV-6 DNAemia was analyzed by a nested PCR method, and the HHV-6-specific lymphocyte proliferation responses were evaluated with a standard lymphocyte proliferation assay. All patients who responded to HHV-6 GS (variant A) antigen also responded to HHV-6 Z29 (variant B) antigen, and a response to HHV-6 Z29 antigen was detected more often than to HHV-6 GS antigen after allo-SCT (P = 0.048). HHV-6 DNA was detected in more patients after than before transplantation (P = 0.01) and in more patients with acute GVHD grades II-IV than those without (P = 0.009). An HHV-6-specific proliferative response was more often detected in patients without, than in those with persistent HHV-6 infection (three consecutively positive PBL samples; P Ͻ 0.001). Patients with persistent HHV-6 infection had lower lymphocyte counts from the 8th week after transplantation than those without (P = 0.03). No HHV-6-specific proliferation responses were detected in the three patients who developed HHV-6 disease. HHV-6 infection was associated with persistent lymphocytopenia and might thereby inhibit immune function.

Specific CD8+T cells recognize human herpesvirus 6B

“…For example, in patients after stem cell transplantation, HHV-6 and CMV reactivation were associated with lymphopenia and reduction in proliferative responses to HHV-6 and CMV [38,39]. However, these results were interpreted in contrasting terms for the two herpesviruses: HHV-6 was supposed to be the causal agent for an immunosuppression that permitted reactivation of this virus and of CMV [38,39]. Only recently, the straightforward alternative explanation has been offered that lymphopenia-associated deficiencies in T cells specific for either virus could be the common cause why either virus may reactivate in transplant patients [40].…”

A rapid monitoring system of human herpesviruses reactivation by LightCycler in stem cell transplantation

“…High levels of HHV-6 in the peripheral blood may correlate with delayed platelet engraftment, as reported by others. 4,24 Isomura et al 25 also reported that the direct effect of HHV-6 on hematopoietic progenitors is one of the major causes of suppression of thrombopoiesis. To date, Bone Marrow Transplantation the pathogenic potential of HHV-6 in SCT recipients is not fully understood.…”

“…Since post-transplant EBV-induced lymphoproliferative disorders (PT-LPD) may arise in the period between the initiation of engraftment and 6-8 mouths post transplant, at which time many patients have defects in T cell function, 4 we should keep following-up all the patients carefully.…”

“…3 Human herpesvirus 6 (HHV-6) is classified into the same subfamily as CMV and ␤ herpesvirus. It has been linked to poor marrow engraftment, 4 encephalitis 5 and interstitial pneumonia, 6 although asymptomatic reactivation of HHV-6 is more common following SCT. 7 Epstein-Barr virus (EBV) is not a major cause of mortality after SCT.…”

Temporal relationship between HHV 6 and graft vs host disease in a patient after haplo-identical SCT and severe T-cell depletion

“…2,4,6 Infection of these cells leads to alteration and modification of immune responses, further facilitating viral replication and creating an environment adept for further viral reactivation. 2,6 Because of the exposure of the recovering immune system to this massive amount of HHV6 Ags, a large number of cells become activated; including the few allo-reactive T cells. 2 This imbalance in immune response promotes the development of GVHD, further enhanced by upregulation of HLA class I and II molecules by the virus.…”