Functional and Epigenetic Studies Reveal Multistep Differentiation and Plasticity of In Vitro-Generated and In Vivo-Derived Follicular T Helper Cells

被引:207
作者
Lu, Kristina T. [1 ]
Kanno, Yuka [2 ]
Cannons, Jennifer L. [1 ]
Handon, Robin [1 ]
Bible, Paul [2 ]
Elkahloun, Abdel G. [1 ]
Anderson, Stacie M. [1 ]
Wei, Lai [2 ]
Sun, Hongwei [2 ]
O'Shea, John J. [2 ]
Schwartzberg, Pamela L. [1 ]
机构
[1] NHGRI, NIH, Bethesda, MD 20892 USA
[2] NIAMSD, NIH, Bethesda, MD 20892 USA
关键词
CENTER B-CELL; MECHANISM DISTINCT; PROVIDE HELP; EXPRESSION; RECEPTOR; IL-21; LINEAGE; ICOS; BCL6; SAP;
D O I
10.1016/j.immuni.2011.07.015
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 T helper (Tfh) cells provide critical help to B cells for germinal center (GC) formation. Mutations affecting SLAM-associated protein (SAP) prevent GC formation because of defective T cell-B cell interactions, yet effects on Tfh cell differentiation remain unclear. We describe the in vitro differentiation of functionally competent "Tfh-like" cells that expressed interleukin-21, Tfh cell markers, and Bcl6 and rescued GC formation in SAP-deficient hosts better than other T helper (Th) cells. SAP-deficient Tfh-like cells appeared virtually indistinguishable from wild-type, yet failed to support GCs in vivo. Interestingly, both Tfh-like and in vivo-derived Tfh cells could produce effector cytokines in response to polarizing conditions. Moreover, Th1, Th2, and Th17 cells could be reprogrammed to obtain Tfh cell characteristics. ChIP-Seq analyses revealed positive epigenetic markings on Tbx21, Gata3, and Rorc in Tfh-like and ex vivo Tfh cells and on Bcl6 in non-Tfh cells, supporting the concept of plasticity between Tfh and other Th cell populations.
引用
收藏
页码:622 / 632
页数:11
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