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Sci Transl Med. 2015 Apr 8;7(282):282ra48. doi: 10.1126/scitranslmed.aaa3700.

Long-lasting stem cell-like memory CD8+ T cells with a naïve-like profile upon yellow fever vaccination.

Author information

1
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.
2
Bioinformatics Core Facility, SIB Swiss Institute of Bioinformatics, Lausanne CH-1015, Switzerland.
3
Department of Oncology, University Hospital of Lausanne (Centre Hospitalier Universitaire Vaudois), Lausanne CH-1011, Switzerland.
4
Service Vaudois de Transfusion Sanguine de la Croix Rouge, Epalinges CH-1066, Switzerland.
5
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.
6
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.

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.

PMID:
25855494
DOI:
10.1126/scitranslmed.aaa3700
[Indexed for MEDLINE]
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