In Vivo RNA Interference Screens Identify Regulators of Antiviral CD4+ and CD8+ T Cell Differentiation

被引：94

作者：

Chen, Runqiang ^{[1
,2
,3
]}

Belanger, Simon ^{[2
]}

Frederick, Megan A. ^{[3
]}

Li, Bin ^{[2
]}

Johnston, Robert J. ^{[2
]}

Xiao, Nengming ^{[4
]}

Liu, Yun-Cai ^{[4
]}

Sharma, Sonia ^{[4
]}

Peters, Bjoern ^{[2
]}

Rao, Anjana ^{[1
]}

Crotty, Shane ^{[2
]}

Pipkin, Matthew E. ^{[3
]}

机构：

[1] La Jolla Inst Allergy & Immunol, Div Signaling & Gene Express, La Jolla, CA 92037 USA

[2] La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA 92037 USA

[3] Scripps Res Inst, Dept Canc Biol, Jupiter, FL 33458 USA

[4] La Jolla Inst Allergy & Immunol, Div Cell Biol, La Jolla, CA 92037 USA

来源：

IMMUNITY | 2014年 / 41卷 / 02期

关键词：

FOLLICULAR HELPER; TRANSCRIPTION FACTORS; IMMUNE-RESPONSES; VIRAL-INFECTION; P-TEFB; MEMORY; EXPRESSION; ELONGATION; EFFECTOR; GENES;

D O I：

10.1016/j.immuni.2014.08.002

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Classical genetic approaches to examine the requirements of genes for T cell differentiation during infection are time consuming. Here we developed a pooled approach to screen 30-100+ genes individually in separate antigen-specific T cells during infection using short hairpin RNAs in a microRNA context (shRNAmir). Independent screens using T cell receptor (TCR)-transgenic CD4+ and CD8+ T cells responding to lymphocytic choriomeningitis virus (LCMV) identifiedmultiple genes that regulated development of follicular helper (Tfh) and T helper 1 (Th1) cells, and short-lived effector and memory precursor cytotoxic T lymphocytes (CTLs). Both screens revealed roles for the positive transcription elongation factor (P-TEFb) component Cyclin T1 (Ccnt1). Inhibiting expression of Cyclin T1, or its catalytic partner Cdk9, impaired development of Th1 cells and protective short-lived effector CTL and enhanced Tfh cell and memory precursor CTL formation in vivo. This pooled shRNA screening approach should have utility in numerous immunological studies.

引用

页码：325 / 338

页数：14

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