A fundamental role for interleukin-21 in the generation of T follicular helper cells

Alexis Vogelzang, Helen N McGuire, Di Yu, Jonathon Sprent, Charles Reay Mackay, Cecile King

Research output: Contribution to journalArticleResearchpeer-review

505 Citations (Scopus)

Abstract

T cell help to B cells is a fundamental property of adaptive immunity, yet only recently have many of the cellular and molecular mechanisms of T cell help emerged. T follicular helper (Tfh) cells are the CD4(+) T helper cells that provide cognate help to B cells for high-affinity antibody production in germinal centers (GC). Tfh cells produce interleukin-21 (IL-21), and we show that IL-21 was necessary for GC formation. However, the central role of IL-21 in GC formation reflected its effects on Tfh cell generation rather than on B cells. Expression of the inducible costimulator (ICOS) was necessary for optimal production of IL-21, indicative of interplay between these two Tfh cell-expressed molecules. Finally, we demonstrate that IL-21 s costimulatory capacity for T helper cell differentiation operated at the level of the T cell receptor signalosome through Vav1, a signaling molecule that controls T cell helper function. This study reveals a previously unappreciated role for Tfh cells in the formation of the GC and isotype switching through a CD4(+) T cell-intrinsic requirement for IL-21.
Original languageEnglish
Pages (from-to)127 - 137
Number of pages11
JournalImmunity
Volume29
Issue number1
DOIs
Publication statusPublished - 2008
Externally publishedYes

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