title: Long-lasting stem cell-like memory CD8+ T cells with a naïve-like profile upon yellow fever vaccination.
abstract: Efficient and persisting immune memory is essential for long-term protection from infectious and malignant diseases. The yellow fever (YF) vaccine is a live attenuated virus that mediates lifelong protection, with recent studies showing that the CD8(+) T cell response is particularly robust. Yet, limited data exist regarding the long-term CD8(+) T cell response, with no studies beyond 5 years after vaccination. We investigated 41 vaccinees, spanning 0.27 to 35 years after vaccination. YF-specific CD8(+) T cells were readily detected in almost all donors (38 of 41), with frequencies decreasing with time. As previously described, effector cells dominated the response early after vaccination. We detected a population of naïve-like YF-specific CD8(+) T cells that was stably maintained for more than 25 years and was capable of self-renewal ex vivo. In-depth analyses of markers and genome-wide mRNA profiling showed that naïve-like YF-specific CD8(+) T cells in vaccinees (i) were distinct from genuine naïve cells in unvaccinated donors, (ii) resembled the recently described stem cell-like memory subset (Tscm), and (iii) among all differentiated subsets, had profiles closest to naïve cells. Our findings reveal that CD8(+) Tscm are efficiently induced by a vaccine in humans, persist for decades, and preserve a naïveness-like profile. These data support YF vaccination as an optimal mechanistic model for the study of long-lasting memory CD8(+) T cells in humans.
authors: Ludwig Cancer Center, University of Lausanne, Epalinges CH-1066, Switzerland. Department of Oncology, University Hospital of Lausanne (Centre Hospitalier Universitaire Vaudois), Lausanne CH-1011, Switzerland.
authors: Silvia A
authors: SA
authors: Fuertes Marraco
authors: Bioinformatics Core Facility, SIB Swiss Institute of Bioinformatics, Lausanne CH-1015, Switzerland.
authors: Charlotte
authors: C
authors: Soneson
authors: Department of Oncology, University Hospital of Lausanne (Centre Hospitalier Universitaire Vaudois), Lausanne CH-1011, Switzerland.
authors: Laurène
authors: L
authors: Cagnon
authors: Department of Oncology, University Hospital of Lausanne (Centre Hospitalier Universitaire Vaudois), Lausanne CH-1011, Switzerland.
authors: Philippe O
authors: PO
authors: Gannon
authors: Department of Oncology, University Hospital of Lausanne (Centre Hospitalier Universitaire Vaudois), Lausanne CH-1011, Switzerland.
authors: Mathilde
authors: M
authors: Allard
authors: Department of Oncology, University Hospital of Lausanne (Centre Hospitalier Universitaire Vaudois), Lausanne CH-1011, Switzerland.
authors: Samia
authors: S
authors: Abed Maillard
authors: Department of Oncology, University Hospital of Lausanne (Centre Hospitalier Universitaire Vaudois), Lausanne CH-1011, Switzerland.
authors: Nicole
authors: N
authors: Montandon
authors: Department of Oncology, University Hospital of Lausanne (Centre Hospitalier Universitaire Vaudois), Lausanne CH-1011, Switzerland.
authors: Nathalie
authors: N
authors: Rufer
authors: Service Vaudois de Transfusion Sanguine de la Croix Rouge, Epalinges CH-1066, Switzerland.
authors: Sophie
authors: S
authors: Waldvogel
authors: Ludwig Cancer Center, University of Lausanne, Epalinges CH-1066, Switzerland. Department of Oncology, University Hospital of Lausanne (Centre Hospitalier Universitaire Vaudois), Lausanne CH-1011, Switzerland. Bioinformatics Core Facility, SIB Swiss Institute of Bioinformatics, Lausanne CH-1015, Switzerland.
authors: Mauro
authors: M
authors: Delorenzi
authors: Ludwig Cancer Center, University of Lausanne, Epalinges CH-1066, Switzerland. Department of Oncology, University Hospital of Lausanne (Centre Hospitalier Universitaire Vaudois), Lausanne CH-1011, Switzerland. doc@dspeiser.ch.
authors: Daniel E
authors: DE
authors: Speiser
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D000939:Epitopes / Q000276:immunology; D020869:Gene Expression Profiling; D006706:Homeostasis; D006801:Humans; D007156:Immunologic Memory; D019409:Interleukin-15 / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000276:immunology; D008875:Middle Aged; D010455:Peptides / Q000276:immunology; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014611:Vaccination; D015004:Yellow Fever / Q000235:genetics / Q000276:immunology* / Q000821:virology; D022341:Yellow Fever Vaccine / Q000276:immunology*; D055815:Young Adult
chemical_list: D000956:Antigens, Viral; D000939:Epitopes; D019409:Interleukin-15; D010455:Peptides; D012333:RNA, Messenger; D022341:Yellow Fever Vaccine