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- W4246138845 abstract "After transplantation (Tx) immunosuppression leads to impaired cellular immune defense resulting in increased risk of viral complications. Post-Tx follow-up of virus-specific T cells (Tvis) may serve as an indicator of viral diseases and overimmunosuppression. Within a prospective longitudinal study we monitored Cytomegalovirus (CMV)- and Adenovirus (ADV)-Tvis in 37 children (1-17 years, median 13 years) during the first year after kidney Tx. Leucocytes were stimulated in vitro with CMV- or ADV-antigen and immunostained by fluorescent antibodies. Based on specific cellular activation and induction of intracellular cytokine production, CMV- and ADV-CD4+ and CD8+Tvis were determined by flow cytometry. In addition viral infections and virus-DNA (PCR) were monitored. CMV- and ADV-CD4+Tvis were permanently detectable and fluctuated depending on the grade of immunosuppression: Under the intensified immunosuppression during the initial post-Tx period we found temporary decrease of CD4+Tvis. When immunosuppression was reduced, Tvis were increasing. In the presence of sufficient numbers of ADV- or CMV-CD4+ Tvis (>2 cells/μl) we did not detect any relevant viral infections or reactivations. Patients with low CD4+Tvis were susceptible for various symptomatic viral infections (e.g. CMV, EBV): The absence of CMV- and ADV-CD4+Tvis (< 2 cells/μl) was correlated with a high risk of EBV-infections/-reactivations with persistence of EBV-DNA (Spearman r= -0.68 and -0.49, p< 0.0001). In case of high EBV-DNA load (>2500 cop/ml) CMV- and ADV-CD4+Tvis were significantly lower than without relevant EBV-DNA-detection (CMV-CD4+Tvis: 1.6±1.3/μl versus 18.8±13.3/μl; p< 0.0001). In contrast to CD4+Tvis, CD8+Tvis were only temporarily detectable. After kidney Tx CMV- and ADV-CD4+Tvis represent not only virus-specific, but also general cellular immune defense: Sufficient levels of CD4+Tvis (>2 cells/μl) prevent from symptomatic viral infections whereas a decrease is associated with an elevated risk of viral complications. Serving as an indicator of overimmunosuppression, monitoring of CD4+Tvis may improve post-Tx management and optimize individual timing of antiviral therapy and dosing of immunosuppression (effect-related drug-monitoring). Recently, we started a prospective controlled randomized trial to verify this hypothesis." @default.
- W4246138845 created "2022-05-12" @default.
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- W4246138845 date "2012-11-01" @default.
- W4246138845 modified "2023-09-24" @default.
- W4246138845 title "Level of Virus-Specific T Cells (Tvis) as an Indicator of Overimmunosuppression after Pediatric Kidney Transplantation" @default.
- W4246138845 doi "https://doi.org/10.1097/00007890-201211271-02371" @default.
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