title: CD40 ligand-expressing recombinant vaccinia virus promotes the generation of CD8(+) central memory T cells.
abstract: Central memory CD8(+) T cells (TCM ) play key roles in the protective immunity against infectious agents, cancer immunotherapy, and adoptive treatments of malignant and viral diseases. CD8(+) TCM cells are characterized by specific phenotypes, homing, and proliferative capacities. However, CD8(+) TCM -cell generation is challenging, and usually requires CD4(+) CD40L(+) T-cell "help" during the priming of naïve CD8(+) T cells. We have generated a replication incompetent CD40 ligand-expressing recombinant vaccinia virus (rVV40L) to promote the differentiation of human naïve CD8(+) T cells into TCM specific for viral and tumor-associated antigens. Soluble CD40 ligand recombinant protein (sCD40L), and vaccinia virus wild-type (VV WT), alone or in combination, were used as controls. Here, we show that, in the absence of CD4(+) T cells, a single "in vitro" stimulation of naïve CD8(+) T cells by rVV40L-infected nonprofessional CD14(+) antigen presenting cells promotes the rapid generation of viral or tumor associated antigen-specific CD8(+) T cells displaying TCM phenotypic and functional properties. These observations demonstrate the high ability of rVV40L to fine tune CD8(+) mediated immune responses, and strongly support the use of similar reagents for clinical immunization and adoptive immunotherapy purposes.
authors.affiliation: Institute of Surgical Research, Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Trella
authors.affiliation: Institute of Surgical Research, Department of Biomedicine, University of Basel, Basel, Switzerland.|Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
authors.forename: Nermin
authors.initials: N
authors.lastname: Raafat
authors.affiliation: Institute of Surgical Research, Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Chantal
authors.initials: C
authors.lastname: Mengus
authors.affiliation: Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Traunecker
authors.affiliation: Institute of Surgical Research, Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Valeria
authors.initials: V
authors.lastname: Governa
authors.affiliation: Department of Visceral Surgery, Kantonspital, Aarau, Switzerland.
authors.forename: Swantje
authors.initials: S
authors.lastname: Heidtmann
authors.affiliation: Institute of Surgical Research, Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Heberer
authors.affiliation: Department of Surgery, University Hospital, Basel, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Oertli
authors.affiliation: Institute of Surgical Research, Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Giulio C
authors.initials: GC
authors.lastname: Spagnoli
authors.affiliation: Institute of Surgical Research, Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Paul
authors.initials: P
authors.lastname: Zajac
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D023201:CD40 Ligand / Q000235:genetics / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines; D002454:Cell Differentiation; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D006801:Humans; D007156:Immunologic Memory; D016219:Immunotherapy, Adoptive / Q000379:methods*; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage; D014616:Vaccinia virus / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D019496:Cancer Vaccines; D014614:Vaccines, Synthetic; D023201:CD40 Ligand
keywords: Antigen presenting cells; CD4+ T cells; CD40-CD40L; CD8+ T cells; Central memory T cells; Immunological memory; Vaccinia virus