Functional and Epigenetic Studies Reveal Multistep Differentiation and Plasticity of In Vitro-Generated and In Vivo-Derived Follicular T Helper Cells
Clicks: 182
ID: 265946
2011
Summary 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.
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schwartzberg2011immunityfunctional
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| Authors | Kristina T. Lu,Yuka Kanno,Jennifer L. Cannons,Robin Handon,Paul Bible,Abdel G. Elkahloun,Stacie M. Anderson,Lai Wei,Hongwei Sun,John J. O'Shea,Pamela L. Schwartzberg;Kristina T. Lu;Yuka Kanno;Jennifer L. Cannons;Robin Handon;Paul Bible;Abdel G. Elkahloun;Stacie M. Anderson;Lai Wei;Hongwei Sun;John J. O'Shea;Pamela L. Schwartzberg; |
| Journal | immunity |
| Year | 2011 |
| DOI | 10.1016/j.immuni.2011.07.015 |
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