IL-7 adjuvant treatment enhances long-term tumor-antigen-specific CD8+ T-cell responses after immunization with recombinant lentivector.
Immunization with recombinant lentivector elicits higher frequencies of tumor antigen-specific memory CD8+ T cells than peptide-based vaccines. This finding correlates with our observation that, upon recombinant lentivector immunization, a higher fraction of antigen-specific effector CD8+ T cells does not down-regulate the expression of the survival/memory marker interleukin-7 receptor alpha chain (IL-7Ralpha). Here we show that, surprisingly, higher expression of IL-7Ralpha on recombinant lentivector-induced effector CD8+ T cells does not result in the up-regulation of survival molecules, such as Bcl-2. We thus hypothesized that physiologic levels of IL-7 might be limiting in vivo for delivering survival signals to the expanding population of effector cells. To test this hypothesis, we administered recombinant IL-7 during the effector phase of the response. We observed an up-regulation of Bcl-2 and a strong expansion of antigen-specific effector CD8+ T cells, and of naive CD8+ T cells. Strikingly, IL-7 treatment elicited also a significant increase in the number of antigen-specific memory CD8+ T cells in recombinant lentivector-immunized mice, but not in peptide-immunized mice. Altogether, these data show that IL-7 adjuvant treatment can enhance long-term antigen-specific CD8+ T-cell responses. However, its efficacy depends on the expression of IL-7Ralpha at the surface of effector CD8+ T cells.
Colombetti
Sara
S
Ludwig Institute for Cancer Research-Lausanne Branch, University of Lausanne, Chemin des Boveresses 155, Epalinges, Switzerland. sara.colombetti@licr.unil.ch
Lévy
Frédéric
F
Chapatte
Laurence
L
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology*; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology*; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology; D015789:HLA-A2 Antigen; D006801:Humans; D007114:Immunization; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D015851:Interleukin-7 / Q000494:pharmacology*; D016086:Lentivirus / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013047:Specific Pathogen-Free Organisms; D037182:T-Cell Antigen Receptor Specificity; D015854:Up-Regulation / Q000187:drug effects; D022223:Vaccines, Subunit / Q000276:immunology*
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; C508605:IL7 protein, human; D015851:Interleukin-7; D019253:Proto-Oncogene Proteins c-bcl-2; D020395:Receptors, Interleukin-7; D011994:Recombinant Proteins; D022223:Vaccines, Subunit; C415350:interleukin-7 receptor, alpha chain; D007371:Interferon-gamma