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Immunity. 2008 Jul 18;29(1):127-37. doi: 10.1016/j.immuni.2008.06.001. Epub 2008 Jul 3.

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

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  • 1Department of Immunology, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia.

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.

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PMID:
18602282
[PubMed - indexed for MEDLINE]
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