The Transcriptional Regulator PLZF Induces the Development of CD44 High Memory Phenotype T Cells

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2008 Nov 14

PMID 19004789

Citations 54

Authors

Julia Raberger

Alexandra Schebesta

Shinya Sakaguchi

Nicole Boucheron

K Emelie M Blomberg

Anna Berglof

Thomas Kolbe

C I Edvard Smith

Thomas Rulicke

Wilfried Ellmeier

Affiliations

Soon will be listed here.

Abstract

Transcriptional pathways controlling the development of CD44(hi) memory phenotype (MP) T cells with "innate-like" functions are not well understood. Here we show that the BTB (bric-a-brac, tramtrack, broad complex) domain-containing protein promyelocytic leukemia zinc finger (PLZF) is expressed in CD44(hi), but not in CD44(lo), CD4(+) T cells. Transgenic expression of PLZF during T cell development and in CD4(+) and CD8(+) T cells induced a T cell intrinsic program leading to an increase in peripheral CD44(hi) MP CD4(+) and CD8(+) T cells and a corresponding decrease of naïve CD44(lo) T cells. The MP CD4(+) and CD8(+) T cells produced IFNgamma upon PMA/ionomycin stimulation, thus showing innate-like function. Changes in the naïve versus memory-like subset distribution were already evident in single-positive thymocytes, indicating PLZF-induced T cell developmental alterations. In addition, CD1d-restricted natural killer T cells in PLZF transgenic mice showed impaired development and were severely reduced in the periphery. Finally, after anti-CD3/CD28 stimulation, CD4(+) transgenic T cells showed reduced IL-2 and IFNgamma production but increased IL-4 secretion as a result of enhanced IL-4 production of the CD44(hi)CD62L(+) subset. Our data indicate that PLZF is a novel regulator of the development of CD44(hi) MP T cells with a characteristic partial innate-like phenotype.

Citing Articles

γδ T, NKT, and MAIT Cells During Evolution: Redundancy or Specialized Functions?.

Harly C, Robert J, Legoux F, Lantz O J Immunol. 2022; 209(2):217-225.

PMID: 35821101 PMC: 7613099. DOI: 10.4049/jimmunol.2200105.

Normalizing and denoising protein expression data from droplet-based single cell profiling.

Mule M, Martins A, Tsang J Nat Commun. 2022; 13(1):2099.

PMID: 35440536 PMC: 9018908. DOI: 10.1038/s41467-022-29356-8.

Hobit and Blimp-1 instruct the differentiation of iNKT cells into resident-phenotype lymphocytes after lineage commitment.

Kragten N, Taggenbrock R, Parga Vidal L, van Lier R, Stark R, van Gisbergen K Eur J Immunol. 2021; 52(3):389-403.

PMID: 34897659 PMC: 9305946. DOI: 10.1002/eji.202149360.

ZBTB Transcription Factors: Key Regulators of the Development, Differentiation and Effector Function of T Cells.

Cheng Z, He T, Gao X, Zhao Y, Wang J Front Immunol. 2021; 12:713294.

PMID: 34349770 PMC: 8326903. DOI: 10.3389/fimmu.2021.713294.

The Timing and Abundance of IL-2Rβ (CD122) Expression Control Thymic NKT Cell Generation and NKT1 Subset Differentiation.

Won H, Kim H, Crossman A, Awasthi P, Gress R, Park J Front Immunol. 2021; 12:642856.

PMID: 34054809 PMC: 8161506. DOI: 10.3389/fimmu.2021.642856.

References

Lambolez F, Kronenberg M, Cheroutre H . Thymic differentiation of TCR alpha beta(+) CD8 alpha alpha(+) IELs. Immunol Rev. 2007; 215:178-88. DOI: 10.1111/j.1600-065X.2006.00488.x. View

Urdahl K, Sun J, Bevan M . Positive selection of MHC class Ib-restricted CD8(+) T cells on hematopoietic cells. Nat Immunol. 2002; 3(8):772-9. PMC: 2782383. DOI: 10.1038/ni814. View

Griewank K, Borowski C, Rietdijk S, Wang N, Julien A, Wei D . Homotypic interactions mediated by Slamf1 and Slamf6 receptors control NKT cell lineage development. Immunity. 2007; 27(5):751-62. PMC: 2170879. DOI: 10.1016/j.immuni.2007.08.020. View

Rodgers J, Cook R . MHC class Ib molecules bridge innate and acquired immunity. Nat Rev Immunol. 2005; 5(6):459-71. DOI: 10.1038/nri1635. View

Rulicke T . Pronuclear microinjection of mouse zygotes. Methods Mol Biol. 2004; 254:165-94. DOI: 10.1385/1-59259-741-6:165. View

Swain S, Agrewala J, Brown D, Jelley-Gibbs D, Golech S, Huston G . CD4+ T-cell memory: generation and multi-faceted roles for CD4+ T cells in protective immunity to influenza. Immunol Rev. 2006; 211:8-22. PMC: 2266984. DOI: 10.1111/j.0105-2896.2006.00388.x. View

Bilic I, Ellmeier W . The role of BTB domain-containing zinc finger proteins in T cell development and function. Immunol Lett. 2006; 108(1):1-9. DOI: 10.1016/j.imlet.2006.09.007. View

Ma A, Koka R, Burkett P . Diverse functions of IL-2, IL-15, and IL-7 in lymphoid homeostasis. Annu Rev Immunol. 2006; 24:657-79. DOI: 10.1146/annurev.immunol.24.021605.090727. View

Li W, Sofi M, Rietdijk S, Wang N, Terhorst C, Chang C . The SLAM-associated protein signaling pathway is required for development of CD4+ T cells selected by homotypic thymocyte interaction. Immunity. 2007; 27(5):763-74. PMC: 2757291. DOI: 10.1016/j.immuni.2007.10.008. View

10.

MacDonald H, Mycko M . Development and selection of Valpha l4i NKT cells. Curr Top Microbiol Immunol. 2007; 314:195-212. View

11.

Stockinger B, Kassiotis G, Bourgeois C . Homeostasis and T cell regulation. Curr Opin Immunol. 2004; 16(6):775-9. DOI: 10.1016/j.coi.2004.09.003. View

12.

Kelly K, Daniel J . POZ for effect--POZ-ZF transcription factors in cancer and development. Trends Cell Biol. 2006; 16(11):578-87. DOI: 10.1016/j.tcb.2006.09.003. View

13.

Kronenberg M, Engel I . On the road: progress in finding the unique pathway of invariant NKT cell differentiation. Curr Opin Immunol. 2007; 19(2):186-93. DOI: 10.1016/j.coi.2007.02.009. View

14.

Prlic M, Williams M, Bevan M . Requirements for CD8 T-cell priming, memory generation and maintenance. Curr Opin Immunol. 2007; 19(3):315-9. DOI: 10.1016/j.coi.2007.04.010. View

15.

Broussard C, Fleischacker C, Fleischecker C, Horai R, Chetana M, Venegas A . Altered development of CD8+ T cell lineages in mice deficient for the Tec kinases Itk and Rlk. Immunity. 2006; 25(1):93-104. DOI: 10.1016/j.immuni.2006.05.011. View

16.

Felices M, Berg L . The Tec kinases Itk and Rlk regulate NKT cell maturation, cytokine production, and survival. J Immunol. 2008; 180(5):3007-18. DOI: 10.4049/jimmunol.180.5.3007. View

17.

Hu J, Sahu N, Walsh E, August A . Memory phenotype CD8+ T cells with innate function selectively develop in the absence of active Itk. Eur J Immunol. 2007; 37(10):2892-9. PMC: 2770953. DOI: 10.1002/eji.200737311. View

18.

Savage A, Constantinides M, Han J, Picard D, Martin E, Li B . The transcription factor PLZF directs the effector program of the NKT cell lineage. Immunity. 2008; 29(3):391-403. PMC: 2613001. DOI: 10.1016/j.immuni.2008.07.011. View

19.

Bendelac A, Savage P, Teyton L . The biology of NKT cells. Annu Rev Immunol. 2006; 25:297-336. DOI: 10.1146/annurev.immunol.25.022106.141711. View

20.

Collins T, Stone J, Williams A . All in the family: the BTB/POZ, KRAB, and SCAN domains. Mol Cell Biol. 2001; 21(11):3609-15. PMC: 86980. DOI: 10.1128/MCB.21.11.3609-3615.2001. View