Functional and epigenetic analyses of in vitro-derived IL-21 producing follicular T helper-like cells

Wednesday, October 26, 2011 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center	NIGMS	IMMUNO/INFLAM-15

Authors

• K Lu
• Y Kanno
• J Cannons
• R Handon
• J O'Shea
• P Schwartzberg

Abstract

Follicular T helper cells (Tfh) are critical for providing help to B cells for germinal center (GC) formation. Mutations affecting SLAM-associated protein (SAP) prevent GC formation due to defective T: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 IL-21, Tfh markers, and Bcl6, and rescued GC formation in SAP-deficient hosts significantly better than other T helper (Th) cells. SAP-deficient Tfh-like cells appeared virtually indistinguishable from wildtype, 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, other Th cell populations could be reprogrammed to obtain Tfh characteristics. ChIP-Seq analyses revealed positive epigenetic markings on Tbx21, Gata3, and Rorc in Tfh-like and ex vivo Tfh cells, and Bcl6 in other Th cells, supporting the concept of plasticity between Tfh and other Th populations. Our results provide insight into requirements for differentiation and plasticity of Tfh cells, which are critical for generation of effective long-term humoral immunity.

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