title: Elevated granzyme M-expressing lymphocytes during cytomegalovirus latency and reactivation after allogeneic stem cell transplantation.
abstract: 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, γδT, 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.
authors: Department of Pathology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; Laboratory for Translational Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands. Electronic address: n.bovenschen@umcutrecht.nl.
authors: Niels
authors: N
authors: Bovenschen
authors: Laboratory for Translational Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
authors: Sanne N M
authors: SN
authors: Spijkers
authors: Department of Pathology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; Laboratory for Translational Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
authors: Annette C
authors: AC
authors: Wensink
authors: Laboratory for Translational Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, 3584 EA Utrecht, The Netherlands.
authors: Ingrid M M
authors: IM
authors: Schellens
authors: Department of Pathology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
authors: Robert
authors: R
authors: van Domselaar
authors: Laboratory for Translational Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, 3584 EA Utrecht, The Netherlands.
authors: Debbie
authors: D
authors: van Baarle
mesh_terms: D000328:Adult; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000097:blood / Q000276:immunology*; D005260:Female; D053804:Granzymes / Q000097:blood / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D033581:Stem Cell Transplantation; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014775:Virus Activation; D017735:Virus Latency; D055815:Young Adult
chemical_list: C509218:GZMM protein, human; D053804:Granzymes
keywords: Cytomegalovirus; Cytotoxic lymphocytes; GrB; GrM; Granzyme M; HCMV; SCT; Stem cell transplantation; granzyme B; granzyme M; human cytomegalovirus; stem cell transplantation