Central memory CD8+ T cells derive from stem-like Tcf7hi effector cells in the absence of cytotoxic differentiation

被引：131

作者：

Ferreira, Daniela Pais ^{[1
]}

Silva, Joana Gomes ^{[1
]}

Wyss, Tania ^{[2
]}

Marraco, Silvia A. Fuertes ^{[1
]}

Scarpellino, Leonardo ^{[3
]}

Charmoy, Melanie ^{[1
]}

Maas, Roeltje ^{[1
,4
,5
]}

Siddiqui, Imran ^{[1
]}

Tang, Li ^{[6
]}

Joyce, Johanna A. ^{[1
,4
]}

Delorenzi, Mauro ^{[1
,2
]}

Luther, Sanjiv A. ^{[3
]}

Speiser, Daniel E. ^{[1
]}

Held, Werner ^{[1
]}

机构：

[1] Univ Lausanne, Dept Oncol, CH-1066 Epalinges, Switzerland

[2] SIB Swiss Inst Bioinformat, Bioinformat Core Facil, CH-1015 Lausanne, Switzerland

[3] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland

[4] Univ Lausanne, Ludwig Inst Canc Res, Lausanne, Switzerland

[5] CHU Vaudois, Neurosci Res Ctr, Dept Neurosci, Lausanne, Switzerland

[6] Ecole Polytech Fed Lausanne, Inst Bioengn, CH-1015 Lausanne, Switzerland

来源：

IMMUNITY | 2020年 / 53卷 / 05期

基金：

瑞士国家科学基金会;

关键词：

CHROMATIN ACCESSIBILITY; INFLAMMATORY CYTOKINES; EPIGENETIC CONTROL; QUALITY-CONTROL; EXPRESSION; PATHWAY; SET; REPRESSION; GENERATION; PRECURSOR;

D O I：

10.1016/j.immuni.2020.09.005

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Central memory CD8(+) T cells (Tcm) control systemic secondary infections and can protect from chronic infection and cancer as a result of their stem-cell-like capacity to expand, differentiate, and self-renew. Central memory is generally thought to emerge following pathogen clearance and to form based on the de-differentiation of cytolytic effector cells. Here, we uncovered rare effector-phase CD8(+) T cells expressing high amounts of the transcription factor Tcf7 (Tcf1) that showed no evidence of prior cytolytic differentiation and that displayed key hallmarks of Tcm cells. These effector-phase Tcf7(hi) cells quantitatively yielded Tcm cells based on lineage tracing. Mechanistically, Tcf1 counteracted the differentiation of Tcf7(hi) cells and sustained the expression of conserved adult stem-cell genes that were critical for CD8(+) T cell stemness. The discovery of stem-cell-like CD8(+) T cells during the effector response to acute infection provides an opportunity to optimize Tcm cell formation by vaccination.

引用

页码：985 / +

页数：27

共 68 条

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