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Previous mouse and human studies have demonstrated that direct IFN-α/β signaling on naive CD8 T cells is critical to support their expansion and acquisition of effector functions. In this study, we show that human naive CD8 T cells primed in the presence of IFN-α possess a heightened ability to respond to homeostatic cytokines and to secondary Ag stimulation, but rather than differentiating to effector or memory CTLs, they preserve nature-like phenotypic features. These are qualities associated with greater efficacy in adoptive immunotherapy. In a mouse model of adoptive transfer, CD8 T cells primed in the presence of IFN-α are able to persist and to mediate a robust recall response even after a long period of naturally driven homeostatic maintenance. The long-lasting persistence of IFN-α-primed CD8 T cells is favored by their enhanced responsiveness to IL-15 and IL-7, as demonstrated in IL-15(-/-) and IL-7(-/-) recipient mice. In humans, exposure to IFN-α during in vitro priming of naive HLA-A2(+) CD8 T cells with autologous dendritic cells loaded with MART1(26-35) peptide renders CD8 T cells with an improved capacity to respond to homeostatic cytokines and to specifically lyse MART1-expressing melanoma cells. Furthermore, in a mouse model of melanoma, adoptive transfer of tumor-specific CD8 T cells primed ex vivo in the presence of IFN-α exhibits an improved ability to contain tumor progression. Therefore, exposure to IFN-α during priming of naive CD8 T cells imprints decisive information on the expanded cells that can be exploited to improve the efficacy of adoptive T cell therapy.

Original publication




Journal article


Journal of immunology (Baltimore, Md. : 1950)

Publication Date





3299 - 3310


Division of Gene Therapy and Hepatology, Center for Applied Medical Research, University of Navarra, Pamplona 31008, Spain.


CD8-Positive T-Lymphocytes, T-Lymphocytes, Cytotoxic, Cells, Cultured, Animals, Mice, Inbred C57BL, Mice, Transgenic, Mice, Knockout, Humans, Mice, Melanoma, Experimental, Interferon-alpha, Interleukin-15, Interleukin-17, Antigens, Cytokines, Adoptive Transfer, Immunization, Secondary, Lymphocyte Activation, Signal Transduction, Immunologic Memory, Homeostasis