Background. Epstein-Barr virus (EBV) and cytomegalovirus reactivations are frequent complications of hematopoeitic allogeneic stem cell transplantation (SCT) because of a lack of T cell control after immunosuppression. Early diagnosis of reactivation and subsequent preemptive therapy relies on frequent viral load measurement. Additional virus-specific T cell reconstitution data could improve the predictive value of viral load detection for viral complications after transplantation. Here, we studied perforin expression in CD8+ T cells as a measure of cytotoxic T cell capacity in relation to the occurrence of viral reactivation. Methods. In a prospective study, we monitored 40 patients during the first 3 months after transplantation and measured viral loads in combination with intracellular perforin expression in CD8+ T cells. Results. Median perforin expression in CD8+ T cells throughout follow-up was higher in patients with viral reactivations than in patients without viral reactivations (4.9% vs 2.3%; P = .001). The median percentage of perforin-expressing CD8+ T cells in patients with high viral reactivations exceeding 1000 copies/mL (10.7%) was statistically significantly higher than that in patients with minor reactivations of 50-1000 copies (4.0%), that in patients with detectable EBV loads that did not exceed the detection limit of 50 copies/mL (2.9%), and that in patients without reactivations (0.8%). Patients with high viral reactivations reached a high percentage of perforinexpressing CD8+ T cells (>10.2%) more often and faster than did patients with low viral loads (≤1000 copies/mL) or without viral reactivations. High perforin expression preceded high viral loads. Conclusion. Perforin-expressing CD8+ T cells may be useful as an easy-to-measure prognostic marker for identifying patients at risk for severe viral reactivation very soon after SCT.

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Keywords CD8+ T lymphocyte, adult, aged, allogeneic stem cell transplantation, article, clinical article, cytotoxic T lymphocyte, disease severity, female, herpes virus infection, human, male, perforin, priority journal, prognosis, protein expression, virus load, virus reactivation
Persistent URL,
Journal Clinical Infectious Diseases
Pietersma, F.L, van Dorp, S, jacobi, R, Ran, L, Nanlohy, N.M, Schuurman, R, … van Baarle, D. (2010). High level of perforin expression in T cells: An early prognostic marker of the severity of herpesvirus reactivation after allogeneic stem cell transplantation in adults. Clinical Infectious Diseases, 50(5), 717–725. doi:10.1086/650455