Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Schwarz,C.
HHV-6-specific T-cell immune reconstitution among
children and adolescents after allogeneic stem cell
transplantation
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [Dissertation] Medical University of Graz;2019. pp. 96
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Schwinger Wolfgang
- Strenger Volker
- Strohmaier Heimo
- Altmetrics:
- Abstract:
- 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. T-lymphocytes play an important role in the control of virus reactivations. The incidence of viral reactivations after HSCT is high, often due to a lack of virus-specific T-cell immune responses. The aim of this project is the description of the HHV-6 specific cellular immunity in children and adolescents after allogeneic HSCT. 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. 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, 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. The virus-specific immunity of patients to HHV-6 was compared to the virus-specific immunity of children and adolescents of a control group. In the control group significantly higher frequencies of HHV-6-specific TNF-α producing CD8+ T-cells were detected in individuals older than 10 years of age [<10 years, median age 6.6 (range 3.1–9.2) and 10–18 years, median age 17.2 (range 10.5–18.3)] (p = 0.033) and the frequencies of HHV-6 specific TNF-α producing CD8+ T-cells positively correlated with the age of the individuals (r= 0.465). In the patient group, there were significant higher frequencies of triple positive CD8+ T-cells (IL-2/TNF-α/IFN-γ) [1.86% (0.38-4.5) vs. 0.93% (0-8.75), p= 0.034] and double positive CD8+ T-cells (IL-2/TNF-α) [1.89% (0.21-5) vs. 1% (0-8.75); p= 0.040] in patients in the second year after HSCT compared to patients in the first year after HSCT. Furthermore, patients during the first year after HSCT had significant lower frequencies of CD8+ T-cells (TNF-α) compared to the control group [1.34% (0.03-13.29) vs. 2.1% (0.72-9.83); p= 0.022]. No differences in the frequencies of HHV-6 specific CD8+ T-cells between the patients in the second year after HSCT and the control group were observed. In the first year after HSCT patients without reactivation had significant higher frequencies of CD4+ specific HHV-6 T-cells (IL-2/TNF-α/IFN-γ and IFN-γ/IL-2) compared to patients with HHV-6 reactivation during the first year after HSCT [1.44% (0.2-19.33) vs. 0.98% (0-3.54); p= 0.048 and 2% (0.17-7.11) vs. 0.99% (0-3.54); p= 0.022]. In the second year after HSCT there were no significant differences in the frequencies of HHV-6 specific T-cells neither for CD4+ nor for CD8+ HHV-6 specific T-cells between the two groups (non-reactivated /reactivated). Significantly higher frequencies of HHV-6 specific CD4+ T-cells (IL-2/TNF-α and IFN-γ/IL-2/TNF-α) in patients without virus reactivation up to 2 years after HSCT in comparison to patients with HHV-6 reactivation during the first year after HSCT were observed [1.69% (0.17-7.11) vs. 0.99% (0-3.54); p= 0.021 and 1.63% (0.38-10.17) vs. 1.55% (0-4.22); p= 0.047]. Significantly higher frequencies of HHV-6 specific CD8+ T-cells (IL-2/TNF-α/IFN-γ) were observed in the control group in comparison to patients with HHV-6 reactivation in the first year after HSCT [1.29% (0.6-7) vs. 0.61% (0.02-2.8); p= 0.048]. Virus-specific T-cells are important effector cells in the control of viral infections. Our results indicate differences in the T-cell immune response against HHV-6 in controls and patients with/ without HHV-6 reactivation up to 2 years after allogeneic HSCT.