TCF1 Expression Marks Self-renewing Human CD8 T Cells

Overview

Journal Blood Adv

Specialty Hematology

Date 2018 Jul 20

PMID 30021780

Citations 70

Authors

Radomir Kratchmarov

Arthur M Magun

Steven L Reiner

Affiliations

Soon will be listed here.

Abstract

Expression of the transcription factor T-cell factor 1 (TCF1) identifies antigen-experienced murine CD8 T cells that retain potential for lymphoid recirculation and the ability to self-renew while producing more differentiated effector cells. We found that CD8 T cells in the blood of both healthy and chronically infected humans expressed TCF1 at 3 distinct levels: high (TCF1-hi), intermediate (TCF1-int), and low (TCF1-lo). TCF1-hi cells could be found within both the naive and memory compartments and were characterized by relative quiescence and lack of immediate effector function. A substantial fraction of TCF1-int cells were found among memory cells, and TCF1-int cells exhibited robust immediate effector functions. TCF1-lo cells were most enriched in effector memory cells that expressed the senescence marker CD57. Following reactivation, TCF1-hi cells gave rise to TCF1-lo descendants while self-renewing the TCF1-hi progenitor. By contrast, reactivation of TCF1-lo cells produced more TCF1-lo cells without evidence of de-differentiating into TCF1-hi cells. Flow cytometric analyses of TCF1 expression from patient specimens may become a useful biomarker for adaptive immune function in response to vaccination, infection, autoimmunity, and cancer.

Citing Articles

Cytotoxic KLRG1+ IL-7R- effector CD8+ T cells distinguish kidney transplant recipients controlling cytomegalovirus reactivation.

Sun Y, Sen S, Parmar R, Arakawa-Hoyt J, Cappelletti M, Rossetti M Front Immunol. 2025; 16:1542531.

PMID: 40028342 PMC: 11868092. DOI: 10.3389/fimmu.2025.1542531.

Transcriptional control of T cell tissue adaptation and effector function in infants and adults.

Szabo P, Levitin H, Connors T, Chen D, Jin J, Thapa P bioRxiv. 2025; .

PMID: 39974963 PMC: 11838503. DOI: 10.1101/2025.02.01.636039.

Circulating memory T cells and TCF1 T cells aid in diagnosis and monitor disease activity in vitiligo.

Wang X, Chen J, Wu W, Fan J, Huang L, Sun W J Pharm Anal. 2024; 14(11):100998.

PMID: 39698313 PMC: 11652857. DOI: 10.1016/j.jpha.2024.100998.

IL15/IL15Rα complex induces an anti-tumor immune response following radiation therapy only in the absence of Tregs and fails to induce expansion of progenitor TCF1+ CD8 T cells.

Piper M, Gadwa J, Hodgson C, Knitz M, Yee E, Zhu Y bioRxiv. 2024; .

PMID: 39345626 PMC: 11429847. DOI: 10.1101/2024.09.18.613691.

Resident memory T cells and cancer.

Gavil N, Cheng K, Masopust D Immunity. 2024; 57(8):1734-1751.

PMID: 39142275 PMC: 11529779. DOI: 10.1016/j.immuni.2024.06.017.

References

Lin W, Nish S, Yen B, Chen Y, Adams W, Kratchmarov R . CD8 T Lymphocyte Self-Renewal during Effector Cell Determination. Cell Rep. 2016; 17(7):1773-1782. PMC: 5108530. DOI: 10.1016/j.celrep.2016.10.032. View

Delpoux A, Hess Michelini R, Verma S, Lai C, Omilusik K, Utzschneider D . Continuous activity of Foxo1 is required to prevent anergy and maintain the memory state of CD8 T cells. J Exp Med. 2017; 215(2):575-594. PMC: 5789410. DOI: 10.1084/jem.20170697. View

Brenchley J, Karandikar N, Betts M, Ambrozak D, Hill B, Crotty L . Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8+ T cells. Blood. 2002; 101(7):2711-20. DOI: 10.1182/blood-2002-07-2103. View

Pearce E, Mullen A, Martins G, Krawczyk C, Hutchins A, Zediak V . Control of effector CD8+ T cell function by the transcription factor Eomesodermin. Science. 2003; 302(5647):1041-3. DOI: 10.1126/science.1090148. View

Huang A, Postow M, Orlowski R, Mick R, Bengsch B, Manne S . T-cell invigoration to tumour burden ratio associated with anti-PD-1 response. Nature. 2017; 545(7652):60-65. PMC: 5554367. DOI: 10.1038/nature22079. View

Germar K, Dose M, Konstantinou T, Zhang J, Wang H, Lobry C . T-cell factor 1 is a gatekeeper for T-cell specification in response to Notch signaling. Proc Natl Acad Sci U S A. 2011; 108(50):20060-5. PMC: 3250146. DOI: 10.1073/pnas.1110230108. View

Mahnke Y, Brodie T, Sallusto F, Roederer M, Lugli E . The who's who of T-cell differentiation: human memory T-cell subsets. Eur J Immunol. 2013; 43(11):2797-809. DOI: 10.1002/eji.201343751. View

Stelekati E, Shin H, Doering T, Dolfi D, Ziegler C, Beiting D . Bystander chronic infection negatively impacts development of CD8(+) T cell memory. Immunity. 2014; 40(5):801-13. PMC: 4114317. DOI: 10.1016/j.immuni.2014.04.010. View

Lin W, Adams W, Nish S, Chen Y, Yen B, Rothman N . Asymmetric PI3K Signaling Driving Developmental and Regenerative Cell Fate Bifurcation. Cell Rep. 2015; 13(10):2203-18. PMC: 4685001. DOI: 10.1016/j.celrep.2015.10.072. View

10.

Willinger T, Freeman T, Herbert M, Hasegawa H, McMichael A, Callan M . Human naive CD8 T cells down-regulate expression of the WNT pathway transcription factors lymphoid enhancer binding factor 1 and transcription factor 7 (T cell factor-1) following antigen encounter in vitro and in vivo. J Immunol. 2006; 176(3):1439-46. DOI: 10.4049/jimmunol.176.3.1439. View

11.

Wu T, Ji Y, Moseman E, Xu H, Manglani M, Kirby M . The TCF1-Bcl6 axis counteracts type I interferon to repress exhaustion and maintain T cell stemness. Sci Immunol. 2016; 1(6). PMC: 5179228. DOI: 10.1126/sciimmunol.aai8593. View

12.

Chu H, Chan S, Gosling J, Blanchard N, Tsitsiklis A, Lythe G . Continuous Effector CD8(+) T Cell Production in a Controlled Persistent Infection Is Sustained by a Proliferative Intermediate Population. Immunity. 2016; 45(1):159-71. PMC: 4956557. DOI: 10.1016/j.immuni.2016.06.013. View

13.

Zhou X, Xue H . Cutting edge: generation of memory precursors and functional memory CD8+ T cells depends on T cell factor-1 and lymphoid enhancer-binding factor-1. J Immunol. 2012; 189(6):2722-6. PMC: 3437003. DOI: 10.4049/jimmunol.1201150. View

14.

Utzschneider D, Charmoy M, Chennupati V, Pousse L, Pais Ferreira D, Calderon-Copete S . T Cell Factor 1-Expressing Memory-like CD8(+) T Cells Sustain the Immune Response to Chronic Viral Infections. Immunity. 2016; 45(2):415-27. DOI: 10.1016/j.immuni.2016.07.021. View

15.

Akondy R, Fitch M, Edupuganti S, Yang S, Kissick H, Li K . Origin and differentiation of human memory CD8 T cells after vaccination. Nature. 2017; 552(7685):362-367. PMC: 6037316. DOI: 10.1038/nature24633. View

16.

Youngblood B, Hale J, Kissick H, Ahn E, Xu X, Wieland A . Effector CD8 T cells dedifferentiate into long-lived memory cells. Nature. 2017; 552(7685):404-409. PMC: 5965677. DOI: 10.1038/nature25144. View

17.

Leong Y, Chen Y, Ong H, Wu D, Man K, Deleage C . CXCR5(+) follicular cytotoxic T cells control viral infection in B cell follicles. Nat Immunol. 2016; 17(10):1187-96. DOI: 10.1038/ni.3543. View

18.

Weber B, Chi A, Chavez A, Yashiro-Ohtani Y, Yang Q, Shestova O . A critical role for TCF-1 in T-lineage specification and differentiation. Nature. 2011; 476(7358):63-8. PMC: 3156435. DOI: 10.1038/nature10279. View

19.

Mazzucchelli R, Durum S . Interleukin-7 receptor expression: intelligent design. Nat Rev Immunol. 2007; 7(2):144-54. DOI: 10.1038/nri2023. View

20.

Im S, Hashimoto M, Gerner M, Lee J, Kissick H, Burger M . Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy. Nature. 2016; 537(7620):417-421. PMC: 5297183. DOI: 10.1038/nature19330. View