Elevated granzyme M-expressing lymphocytes during cytomegalovirus latency and reactivation after allogeneic stem cell transplantation

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• 作者：Niels Bovenschen ; Sanne N.M. Spijkers ; Annette C. Wensink ; Ingrid M.M. Schellens ; Robert van Domselaar ; Debbie van Baarle
• 关键词：HCMV ; human cytomegalovirus ; SCT ; stem cell transplantation ; GrM ; granzyme M ; GrB ; granzyme B
• 刊名：Clinical Immunology
• 出版年：January, 2014
• 年：2014
• 卷：150
• 期：1
• 页码：1-11
• 全文大小：1529 K

文摘

Human cytomegalovirus (HCMV) reactivation can cause serious complications in allogeneic stem cell transplantation (SCT) patients. HCMV is controlled by cytotoxic lymphocytes that release antiviral granzymes. Recently, we have demonstrated that granzyme M (GrM) inhibits HCMV replication in vitro, however the physiological role of GrM and its cellular distribution during HCMV infection remains unknown. Here, we examined GrM expression in lymphocyte populations during HCMV infection. The percentage of GrM-expressing effector-memory CD4⁺ T-cells was higher in HCMV latently-infected healthy individuals compared to that of uninfected individuals. SCT recipients had higher percentages of GrM-expressing CD4⁺ T, CD8⁺ T, 纬未T, and NKT cells. Despite lower total T-cell numbers, HCMV reactivation in SCT patients specifically associated with higher percentages of GrM-expressing CD4⁺ (total and central-memory) T-cells. GrM was elevated in plasma during HCMV reactivation, pointing to extracellular perforin-independent functions of GrM. We conclude that GrM may be important in regulating HCMV latency and reactivation in SCT patients.