CD40 ligand‐expressing recombinant vaccinia virus promotes the generation of CD8+ central memory T cells |
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Authors: | Emanuele Trella Nermin Raafat Chantal Mengus Emmanuel Traunecker Valeria Governa Swantje Heidtmann Michael Heberer Daniel Oertli Giulio C Spagnoli Paul Zajac |
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Institution: | 1. Institute of Surgical Research, Department of Biomedicine, University of Basel, Basel, Switzerland;2. Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt;3. Department of Biomedicine, University of Basel, Basel, Switzerland;4. Department of Visceral Surgery, Kantonspital, Aarau, Switzerland;5. Department of Surgery, University Hospital, Basel, Switzerland |
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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. |
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Keywords: | Antigen presenting cells Central memory T  cells CD40‐CD40L CD4+ T  cells CD8+ T  cells Immunological memory Vaccinia virus |
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