Mechanistic insight into the induction of liver tissue-resident memory CD8+ T cells by glycolipid-peptide vaccination
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<sup>+</sup> 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<sup>+</sup> 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.
Authors
- Mitch Ganley (ORCID: https://orcid.org/0000-0001-6064-552X)
- DORIS J. HIRSCHMANN
- Benjamin J. Compton (ORCID: https://orcid.org/0000-0002-5245-9767)
- Ian F. Hermans (ORCID: https://orcid.org/0000-0002-7584-887X)
- Sarah L. Draper (ORCID: https://orcid.org/0000-0001-8330-121X)
- Dhilshan Jayasinghe
- Sage Robinson (ORCID: https://orcid.org/0000-0001-8571-9003)
- Mireille H. Lahoud (ORCID: https://orcid.org/0000-0001-8472-6201)
- Kirsteen M. Tullett (ORCID: https://orcid.org/0000-0002-2389-9819)
- Yu Cheng Chua (ORCID: https://orcid.org/0000-0002-7260-5282)
- Zhengyu Ge (ORCID: https://orcid.org/0000-0002-8735-5335)
- William R. Heath (ORCID: https://orcid.org/0000-0001-9670-259X)
- A. Lee
- Lauren E. Holz (ORCID: https://orcid.org/0000-0003-4897-0981)
- Peck Szee Tan (ORCID: https://orcid.org/0000-0002-8808-7125)
- David S. Larsen (ORCID: https://orcid.org/0000-0002-3563-1086)
- Geoffrey I. McFadden (ORCID: https://orcid.org/0000-0002-5351-1627)
- Tsuneyasu Kaisho (ORCID: https://orcid.org/0000-0003-2616-1665)
- Irina Caminschi (ORCID: https://orcid.org/0000-0002-9027-2098)
- R. J. Anderson (ORCID: https://orcid.org/0000-0003-3467-9202)
- Lynette Beattie (ORCID: https://orcid.org/0000-0002-5794-7233)
- Anton Cozijnsen (ORCID: https://orcid.org/0000-0002-2763-2927)
- Gavin F. Painter (ORCID: https://orcid.org/0000-0002-1310-7769)
- Stéphanie Gras (ORCID: https://orcid.org/0000-0001-7416-038X)
- Maria N. de Menezes (ORCID: https://orcid.org/0000-0003-3231-0620)
- Shirley Le
- Taylah Phabmixay
Institutions
- The University of Melbourne (AU)
- Wakayama Medical University (JP)
- La Trobe University (AU)
- Malaghan Institute of Medical Research (NZ)
- Discovery Institute (US)
- Australian Regenerative Medicine Institute (AU)
- Victoria University of Wellington (NZ)
- Peter Doherty Institute (AU)
- Monash University (AU)
- University of Otago (NZ)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-02-01
- DOI
- https://doi.org/10.1016/j.celrep.2025.115295
- Citations
- 4
- Primary Topic
- Immunotherapy and Immune Responses
- Type
- article
- Field-Weighted Citation Impact
- 3.19
Funders
- Takeda Science Foundation
- Victoria University of Wellington
- Victoria University
- Ministry of Business, Innovation and Employment
- Medical Research Council
- National Health and Medical Research Council
- Health Research Council of New Zealand