Transient inhibition of type I interferon enhances CD8+ T cell stemness and vaccine protection

被引：1

作者：

Broomfield, Benjamin J. ^{[1
,2
]}

Tan, Chin Wee ^{[1
,2
,3
]}

Qin, Raymond Z. ^{[1
,2
]}

Abberger, Hanna ^{[1
,2
]}

Duckworth, Brigette C. ^{[1
,2
]}

Alvarado, Carolina ^{[1
]}

Dalit, Lennard ^{[1
,2
]}

Lee, Chee Leng ^{[4
]}

Shandre Mugan, Rekha ^{[4
]}

Mazrad, Zihnil A. I. ^{[4
]}

Muramatsu, Hiromi ^{[5
]}

Mackiewicz, Liana ^{[1
]}

Williams, Bailey E. ^{[1
]}

Chen, Jinjin ^{[1
,2
]}

Takanashi, Asuka ^{[4
]}

Fabb, Stewart ^{[4
]}

Pellegrini, Marc ^{[6
]}

Rogers, Kelly L. ^{[1
,2
]}

Moon, Woohyun J. ^{[7
]}

Pouton, Colin W. ^{[4
]}

Davis, Melissa J. ^{[1
,3
,8
]}

Nutt, Stephen L. ^{[1
,2
]}

Pardi, Norbert ^{[5
]}

Wimmer, Verena C. ^{[1
,2
]}

Groom, Joanna R. ^{[1
,2
]}

机构：

[1] Walter & Eliza Hall Inst Med Res, Parkville, Australia

[2] Univ Melbourne, Dept Med Biol, Parkville, Australia

[3] Univ Queensland, Frazer Inst, Fac Med, Brisbane, Australia

[4] Monash Univ, Monash Inst Pharmaceut Sci, Drug Delivery Disposit & Dynam, Parkville, Australia

[5] Perelman Sch Med, Dept Microbiol, Philadelphia, PA USA

[6] Centenary Inst Canc Med & Cell Biol, Camperdown, Australia

[7] Acuitas Therapeut, Vancouver, BC, Canada

[8] Univ Adelaide, Fac Hlth & Med Sci, Sch Biomed, Adelaide, Australia

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2025年 / 222卷 / 05期

基金：

英国医学研究理事会;

关键词：

INFLAMMATORY CYTOKINES; EXPRESSION DETERMINES; SELF-RENEWAL; B-CELLS; EFFECTOR; RESPONSES; MICE; IFN; DIFFERENTIATION; INFECTION;

D O I：

10.1084/jem.20241148

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Developing vaccines that promote CD8+ T cell memory is a challenge for infectious disease and cancer immunotherapy. TCF-1+ stem cell-like memory CD8+ T (TSCM) cells are important determinants of long-lived memory. Yet, the developmental requirements for TSCM cell formation are unclear. Here, we identify the temporal window for type I interferon receptor (IFNAR) blockade to drive TSCM cell generation following viral infection and mRNA-lipid nanoparticle vaccination. We reveal a reversible developmental trajectory where transcriptionally distinct TSCM cells emerged from a transitional precursor of exhausted T cellular state concomitant with viral clearance. TSCM cell differentiation correlated with T cell retention within the lymph node paracortex due to disrupted CXCR3 chemokine gradient formation. These effects were linked to increased antigen load and a counterintuitive increase in IFN gamma, which controlled cell location. Vaccination with the IFNAR blockade promoted TSCM cell differentiation and enhanced protection against chronic infection. These findings propose an approach to vaccine design whereby modulation of inflammation promotes memory formation and function.

引用

页数：29

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