Searching for the origin of the enigmatic circulating T follicular helper cells
Savita Pahwa
Savita Pahwa
Published July 2, 2019
Citation Information: J Clin Invest. 2019;129(8):3048-3051. https://doi.org/10.1172/JCI130311.
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Searching for the origin of the enigmatic circulating T follicular helper cells

Abstract

T follicular helper (Tfh) cells in germinal centers of secondary lymphoid organs are pivotal for B and T cell interactions required for induction of humoral immunity. It has long been debated whether Tfh cells exit from lymph nodes into the blood as circulating Tfh cells. In this issue of the JCI, Vella et al. have taken the bull by the horns and applied considerable technical muscle to answer this question. By analyzing phenotype, transcriptome, epigenetic profile, and T cell receptor clonotype, the authors provide evidence that a subset of cTfh cells do indeed originate in lymph nodes and traffic into the blood via the thoracic duct.

Authors

Savita Pahwa

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Figure 1

Schematic representation of GC Tfh cells in lymph nodes, thoracic duct, and circulation.

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Schematic representation of GC Tfh cells in lymph nodes, thoracic duct, ...
Tfh cells in B cell follicles of lymphoid tissue traffic to the GCs, where they provide critical help for B cells. In this issue, Vella et al. identify a population of Tfh cells with high expression of CXCR5 and PD-1 (CXCR5++PD-1++) that is present in both the GC and thoracic duct and has similar transcriptional and phenotypic characteristics in both locations; however, this population was present at a lower frequency in the thoracic duct than in the lymph nodes. cTfh cells with a similar phenotypic profile were also detectable in blood, but in even lower frequencies. An activated subset (ICOS+CD38+) of cTfh cells that are believed to be vaccine responsive, contained cells with similarities to thoracic duct and lymphoid GC Tfh cells. These studies provide evidence that a population of circulatory Tfh cells originated in the GC of lymph nodes, thereby connecting the biology of Tfh cells in blood to Tfh cells in lymphoid tissue.