title: Generation of HCMV-specific T-cell lines from seropositive solid-organ-transplant recipients for adoptive T-cell therapy.
abstract: Chronically immunosuppressed patients, like solid-organ-transplant (SOT) recipients, are at increased risk for severe human cytomegalovirus (HCMV) infection. Despite the availability of effective antiviral drugs, lasting control of remaining viruses is dependent on an effective T-cell immunity. So in some patients conventional antiviral therapy cannot control the infection and prolonged virostatic therapy is limited by its side effects and the development of viral resistance. Selective reconstitution of cellular immunity by adoptive transfer of HCMV-specific T cells derived from healthy donors is a safe and effective approach in hematopoietic stem cell transplant recipients. The aim of this study was to determine whether functional HCMV-specific T cells can also be generated from chronically immunosuppressed patients. Autologous CD4+/8+ T-cell lines directed against the HCMV protein IE-1 were generated from the peripheral blood of SOT patients using a recently developed modular protocol easily applicable to good-manufacturing-practice conditions. T-cell lines from SOT patients showed similar features as cells from healthy donors regarding phenotype, functionality (HCMV-specific killing, gene expression pattern, and cytokine secretion), IE-1 epitope recognition, and dominance of distinct T-cell receptor V beta families. Most importantly, this protocol also allowed the generation of T-cell lines from immunosuppressed patients with HCMV infection/chronic HCMV disease. Our data suggest the potential of this autologous approach for the treatment of SOT recipients suffering from HCMV infection/disease poorly responding to virostatic therapy.
authors.affiliation: Department of Nephrology and Internal Intensive Care, Charité-Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany. gordon.brestrich@charite.de
authors.forename: Gordon
authors.initials: G
authors.lastname: Brestrich
authors.forename: Sandra
authors.initials: S
authors.lastname: Zwinger
authors.forename: Andy
authors.initials: A
authors.lastname: Roemhild
authors.forename: Michel
authors.initials: M
authors.lastname: Noutsias
authors.forename: Maria
authors.initials: M
authors.lastname: Rohde
authors.forename: Kathrin
authors.initials: K
authors.lastname: Keeren
authors.forename: Birgit
authors.initials: B
authors.lastname: Sawitzki
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Petra
authors.initials: P
authors.lastname: Reinke
authors.forename: Markus H
authors.initials: MH
authors.lastname: Hammer
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation / Q000821:virology; D002460:Cell Line; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000628:therapy*; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D018604:Epitope Mapping; D020869:Gene Expression Profiling; D006801:Humans; D017874:Immediate-Early Proteins / Q000276:immunology*; D016219:Immunotherapy, Adoptive; D016030:Kidney Transplantation / Q000276:immunology; D016040:Lung Transplantation / Q000276:immunology
chemical_list: D016207:Cytokines; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins