Differential Requirements for Tcf1 Long Isoforms in CD8 + and CD4 + T Cell Responses to Acute Viral Infection

Jodi A Gullicksrud; Fengyin Li; Shaojun Xing; Zhouhao Zeng; Weiqun Peng; Vladimir P Badovinac; John T Harty; Hai-Hui Xue

doi:10.4049/jimmunol.1700595

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Differential Requirements for Tcf1 Long Isoforms in CD8 + and CD4 + T Cell Responses to Acute Viral Infection

Journal article

Peer reviewed

Differential Requirements for Tcf1 Long Isoforms in CD8 + and CD4 + T Cell Responses to Acute Viral Infection

Jodi A Gullicksrud, Fengyin Li, Shaojun Xing, Zhouhao Zeng, Weiqun Peng, Vladimir P Badovinac, John T Harty and Hai-Hui Xue

The Journal of immunology (1950), Vol.199(3), pp.911-919

08/01/2017

DOI: 10.4049/jimmunol.1700595

PMCID: PMC5531591

PMID: 28652395

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Abstract

In response to acute viral infection, activated naive T cells give rise to effector T cells that clear the pathogen and memory T cells that persist long-term and provide heightened protection. T cell factor 1 (Tcf1) is essential for several of these differentiation processes. Tcf1 is expressed in multiple isoforms, with all isoforms sharing the same HDAC and DNA-binding domains and the long isoforms containing a unique N-terminal β-catenin-interacting domain. In this study, we specifically ablated Tcf1 long isoforms in mice, while retaining expression of Tcf1 short isoforms. During CD8 T cell responses, Tcf1 long isoforms were dispensable for generating cytotoxic CD8 effector T cells and maintaining memory CD8 T cell pool size, but they contributed to optimal maturation of central memory CD8 T cells and their optimal secondary expansion in a recall response. In contrast, Tcf1 long isoforms were required for differentiation of T follicular helper (T ) cells, but not T 1 effectors, elicited by viral infection. Although Tcf1 short isoforms adequately supported Bcl6 and ICOS expression in T cells, Tcf1 long isoforms remained important for suppressing the expression of Blimp1 and T 1-associated genes and for positively regulating Id3 to restrain germinal center T cell differentiation. Furthermore, formation of memory T 1 and memory T cells strongly depended on Tcf1 long isoforms. These data reveal that Tcf1 long and short isoforms have distinct, yet complementary, functions and may represent an evolutionarily conserved means to ensure proper programming of CD8 and CD4 T cell responses to viral infection.

Cell Differentiation

Lymphocytic choriomeningitis virus - immunology

Cytotoxicity Tests, Immunologic

Germinal Center - immunology

Inhibitor of Differentiation Proteins - genetics

Lymphocytic Choriomeningitis - immunology

CD4-Positive T-Lymphocytes - immunology

Lymphocytic choriomeningitis virus - isolation & purification

Proto-Oncogene Proteins c-bcl-6 - metabolism

T Cell Transcription Factor 1 - deficiency

Inducible T-Cell Co-Stimulator Protein - genetics

Germinal Center - cytology

T Cell Transcription Factor 1 - chemistry

Inhibitor of Differentiation Proteins - metabolism

Transcription Factors - genetics

T Cell Transcription Factor 1 - genetics

Proto-Oncogene Proteins c-bcl-6 - genetics

Transcription Factors - metabolism

Animals

Germinal Center - metabolism

Protein Isoforms

T Cell Transcription Factor 1 - immunology

Immunologic Memory

Mice

Inducible T-Cell Co-Stimulator Protein - metabolism

CD8-Positive T-Lymphocytes - immunology

Positive Regulatory Domain I-Binding Factor 1

Details

Title: Subtitle: Differential Requirements for Tcf1 Long Isoforms in CD8 + and CD4 + T Cell Responses to Acute Viral Infection
Creators: Jodi A Gullicksrud - Interdisciplinary Immunology Graduate Program, University of Iowa, Iowa City, IA 52242
Fengyin Li - Department of Microbiology, University of Iowa, Iowa City, IA 52242
Shaojun Xing - Department of Microbiology, University of Iowa, Iowa City, IA 52242
Zhouhao Zeng - Department of Physics, The George Washington University, Washington, DC 20052; and
Weiqun Peng - Department of Physics, The George Washington University, Washington, DC 20052; and
Vladimir P Badovinac - Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242
John T Harty - Interdisciplinary Immunology Graduate Program, University of Iowa, Iowa City, IA 52242
Hai-Hui Xue - Interdisciplinary Immunology Graduate Program, University of Iowa, Iowa City, IA 52242
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.199(3), pp.911-919
DOI: 10.4049/jimmunol.1700595
PMID: 28652395
PMCID: PMC5531591
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Grant note: R01 AI114543 / NIAID NIH HHS R01 AI112579 / NIAID NIH HHS S10 OD016199 / NIH HHS R01 GM113961 / NIGMS NIH HHS R01 AI042767 / NIAID NIH HHS R21 AI042767 / NIAID NIH HHS P30 CA086862 / NCI NIH HHS R21 AI113806 / NIAID NIH HHS R01 AI121080 / NIAID NIH HHS I01 BX002903 / BLRD VA R21 AI119160 / NIAID NIH HHS R37 AI042767 / NIAID NIH HHS R21 AI115149 / NIAID NIH HHS T32 AI007485 / NIAID NIH HHS
Language: English
Date published: 08/01/2017
Academic Unit: Microbiology and Immunology; Pathology
Record Identifier: 9984047742802771

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