CD40 ligandexpressing recombinant vaccinia virus promotes the generation of CD8 central memory Tcells

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 naı̈ve CD8+ T cells. We have generated a replication incompetent CD40 ligand-expressing recombinant vaccinia virus (rVV40L) to promote the differentiation of human naı̈ve 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 naı̈ve 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.