Cell reports · 2025
Mechanistic insight into the induction of liver tissue-resident memory CD8+ T cells by glycolipid-peptide vaccination.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Chua Yu Cheng, Draper Sarah L, Le Shirley, de Menezes Maria N, Ganley Mitch, Ge Zhengyu, Lee Ariane, Phabmixay Taylah, Hirschmann Daria, Robinson Sage A, Tan Peck Szee, Tullett Kirsteen M, Anderson Regan J, Jayasinghe Dhilshan, Cozijnsen Anton, Lahoud Mireille H, Caminschi Irina, Beattie Lynette, McFadden Geoffrey I, Larsen David S, Kaisho Tsuneyasu, Gras Stephanie, Hermans Ian F, Compton Benjamin J, Heath William R, Painter Gavin F, Holz Lauren E
Аннотация
We recently demonstrated that vaccines comprising antigenic peptides conjugated to a glycolipid agonist, termed glycolipid-peptide (GLP) vaccines, efficiently generate substantial numbers of long-lived CD8+ liver-resident memory T (Trm) cells that are crucial for protection against malaria liver-stage infection. To understand the underlying mechanism, we examined the prerequisites for priming, differentiation, and secondary boosting of liver Trm cells using these GLP vaccines. Our study revealed that generation of long-lived liver Trm cells relies on CD8+ T cell priming by type 1 conventional dendritic (cDC1) cells, followed by post-priming exposure to a combination of vaccine-derived inflammatory and antigenic signals. Boosting of liver Trm cells is feasible using the same GLP vaccine, but a substantial delay is required for optimal responses due to natural killer T (NKT) cell anergy. Overall, our study unveils key requirements for the development of long-lived liver Trm cells, offering valuable insights for future vaccine design.