HHV-6-specific T-cell Reconstitution Among Children and Adolescents After Allogeneic Stem.
Condition: Allogeneic Stem Cell Transplantation
Study type: Observational

Summary: 
      Human herpesvirus 6 (HHV-6) causes only minor symptoms in healthy individuals but in
      immunosuppressed patients, e.g., patients after allogeneic stem cell transplantation (HSCT),
      HHV-6 reactivations can lead to diseases in different organ systems. HHV-6 reactivations have
      also been reported to be a cause for delayed engraftment, a trigger of graft-versus-host
      disease and a co-factor for other virus reactivations. T-lymphocytes play an important role
      in the control of virus reactivations. Little is known about the development of
      virus-specific T-cells after allogeneic HSCT.
    

Detailed description: 
      Background:

      Human herpesvirus 6 (HHV-6) causes only minor symptoms in healthy individuals but in
      immunosuppressed patients, e.g., patients after allogeneic stem cell transplantation (HSCT),
      HHV-6 reactivations can lead to diseases in different organ systems. HHV-6 reactivations have
      also been reported to be a cause for delayed engraftment, a trigger of graft-versus-host
      disease and a co-factor for other virus reactivations. T-lymphocytes play an important role
      in the control of virus reactivations. Little is known about the development of
      virus-specific T-cells after allogeneic HSCT.

      Objective:

      The aim of this study was the description of the HHV-6 specific cellular immunity in children
      and adolescents after allogeneic HSCT in the context of the clinical course.

      Study design and participants:

      For this prospective, cross-sectional study, 28 children and adolescents after allogeneic
      HSCT who received follow-up support at the respective centers were included. Patients were
      enrolled up to 24 months after allogeneic HSCT.. Peripheral venous blood was drawn 3, 6, 9,
      12, 18, and 24 months after allogeneic HSCT. Furthermore, a blood sample was taken from 25
      age- and sex-matched healthy controls without any inflammatory, immunological, or infectious
      diseases. This study was approved by the Institutional Review Board of the Medical University
      Graz and patients, parents or legal guardians of patients gave written informed consent in
      accordance with the Declaration of Helsinki.

      Methods:

      3, 6, 9, 12, 18 and 24 months after allogeneic HSCT peripheral blood mononuclear cells were
      isolated from patient blood, stimulated with HHV-6-specific antigen (U54) and cultured for 10
      days. Furthermore, a blood sample was taken from 25 age- and sex-matched healthy controls
      without any inflammatory, immunological, or infectious diseases.

      On day 10, peripheral blood mononuclear cells were re-stimulated with the virus antigen U54
      for 6 hours and, thereafter, stained for surface markers (CD3, CD4, CD8, CD56) and
      intracytoplasmatic activation markers IL-2 (Interleukin-2), IFN-γ (Interferon-γ), TNF-α
      (tumor necrosis factor-α) for flow cytometric detection of virus-specific T-cells. T-cells
      with intracytoplasmic expression of activation markers after stimulation with the virus
      antigen are HHV-6-specific T-cells. This indicated HHV-6 specific cellular immunity.

      The virus-specific immunity of patients to HHV-6 was compared to the virus-specific immunity
      of children and adolescents of a control group.
    

Intervention name(s): Cell cultivation, Antigen testing
Intervention type(s): Other
Intervention description(s): day 10, peripheral blood mononuclear cells were re-stimulated with the virus antigen U54 for 6 hours and, thereafter, stained for surface markers (CD3, CD4, CD8, CD56) and intracytoplasmatic activation markers (IL-2, IFN-γ, TNF-α) for flow cytometric detection of virus-specific T-cells. T-cells with intracytoplasmic expression of activation markers after stimulation with the virus antigen are HHV-6-specific T-cells. This indicated HHV-6 specific cellular immunity.
No more interventions in human except blood sampling, only basic research.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        28 children with adolescent after allogeneic HSCT 25 healthy cildren as control (age and
        sex mached)
      
Biospecimen description: 
      blood sampling
    
Keywords: allogeneic stem cell transplantation; Human herpesvirus 6 (HHV-6); T-lymphocytes; CD4+ or CD8+ T-cells