Bcl6 Expressing Follicular Helper CD4 T Cells Are Fate Committed Early and Have the Capacity To Form Memory

被引:188
作者
Choi, Youn Soo [1 ]
Yang, Jessica A. [1 ]
Yusuf, Isharat [1 ]
Johnston, Robert J. [1 ,2 ]
Greenbaum, Jason [1 ]
Peters, Bjoern [1 ]
Crotty, Shane [1 ,2 ,3 ]
机构
[1] La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA 92037 USA
[2] Univ Calif San Diego, Sch Med, Dept Med, La Jolla, CA 92037 USA
[3] Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA
基金
美国国家卫生研究院;
关键词
CENTER B-CELL; TRANSCRIPTION FACTOR; IMMUNE-RESPONSES; TH2; CELLS; DIFFERENTIATION; EFFECTOR; PLASTICITY; BLIMP-1; REPRESSION; GENERATION;
D O I
10.4049/jimmunol.1202963
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Follicular helper CD4 T (Tfh) cells are a distinct type of differentiated CD4 T cells uniquely specialized for B cell help. In this study, we examined Tfh cell fate commitment, including distinguishing features of Tfh versus Th1 proliferation and survival. Using cell transfer approaches at early time points after an acute viral infection, we demonstrate that early Tfh cells and Th1 cells are already strongly cell fate committed by day 3. Nevertheless, Tfh cell proliferation was tightly regulated in a TCR-dependent manner. The Tfh cells still depend on extrinsic cell fate cues from B cells in their physiological in vivo environment. Unexpectedly, we found that Tfh cells share a number of phenotypic parallels with memory precursor CD8 T cells, including selective upregulation of IL-7R alpha and a collection of coregulated genes. As a consequence, the early Tfh cells can progress to robustly form memory cells. These data support the hypothesis that CD4 and CD8 T cells share core aspects of a memory cell precursor gene expression program involving Bcl6, and a strong relationship exists between Tfh cells and memory CD4 T cell development. The Journal of Immunology, 2013, 190: 4014-4026.
引用
收藏
页码:4014 / 4026
页数:13
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