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

Abstract

One Sentence Summary:The Yellow Fever vaccine induces a CD8 T stem cell-like memory subset that preserves a high degree of "Naïveness" and is stably maintained for over two decades in humans. with no studies beyond five years post-vaccination. 7Hereby, we investigated 41 vaccinees, spanning 0.27 to 35 years after vaccination. YF-8 specific CD8 T cells were readily detected in almost all donors (38/41), with frequencies 9 decreasing with time. As previously described, effector cells dominated the response early 10 after vaccination. We detected a population of Naïve-like YF-specific CD8 T cells that was 11 stably maintained for over 25 years and was capable of self-renewal ex vivo. In-depth 12 analyses of markers and genome-wide mRNA profiling showed that Naïve-like YF-specific 13 CD8 T cells in vaccinees: i) were distinct from genuine Naïve cells in unvaccinated donors 14 ii) resembled the recently described stem cell-like memory subset (Tscm), and iii) amongst 15 all differentiated subsets, had profiles closest to the Naïve. Our findings reveal that CD8 16 Tscm are efficiently induced by a vaccine in humans, persist for decades and preserve a 17 particularly high degree of "Naïveness". This supports YF vaccination as an optimal 18 mechanistic model for the study of long-lasting memory CD8 T cells in humans.

Phenotype and function of HBV-specific T cells is determined by the targeted epitope in addition to the stage of infection

“…We studied each HBV-specific T cell response in its entirety, including naïve-like T cells 36. The median percentage of cells expressing each marker in the three infection stages is presented in figure 4 for both core 18 and pol 455 -specific T cells, with additional data on relative expression levels for select markers.…”

The Antitumor Effects of Vaccine-Activated CD8+ T Cells Associate with Weak TCR Signaling and Induction of Stem-Like Memory T Cells

“…They further found that human Tscm mediated strong antitumor effect in mice bearing human tumors (43). In a retrospective study, Speiser and colleagues found that yellow fever vaccine-induced Tscm in human correlated to long-term protection (44). Here we show that cancer vaccine can elicit Tscm in vivo , which is associated with TCR downregulation and weak TCR signaling, and correlates with stronger antitumor effect.…”

Role of memory T cell subsets for adoptive immunotherapy

“…2). Concerning the in vivo persistence of these relatively undifferentiated memory subsets in humans the group of Daniel Speiser recently provided impressive data showing that T cells specific to yellow fever virus could be found in individuals up to 35 years after vaccination [38]. Another recent study used sequencing of specific integration sites to follow the long-term persistence of genetically modified T cell subsets after donor lymphocyte infusion [39].…”