Iyer, S.S. et al. Identification of novel markers for mouse CD4(+) T follicular helper cells. Eur. J. Immunol. 43, 3219-3232

Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA
European Journal of Immunology (Impact Factor: 4.03). 12/2013; 43(12). DOI: 10.1002/eji.201343469
Source: PubMed


CD4(+) T-follicular helper (TFH ) cells are central for generation of long-term B-cell immunity. A defining phenotypic attribute of TFH cells is the expression of the chemokine receptor CXCR5, and TFH cells are typically identified by co-expression of CXCR5 together with other markers such as programmed cell death (PD)-1. Herein we report high-level expression of the nutrient transporter folate receptor 4 (FR4) on TFH cells in acute viral infection. Distinct from the expression profile of conventional TFH markers, FR4 was highly expressed by naive CD4(+) T cells, was downregulated after activation and subsequently re-expressed on TFH cells. Furthermore, FR4 expression was maintained, albeit at lower levels, on memory TFH cells. Comparative gene expression profiling of FR4(hi) versus FR4(lo) antigen-specific CD4(+) effector T cells revealed a molecular signature consistent with TFH and TH 1 subsets respectively. Interestingly, genes involved in the purine metabolic pathway, including the ecto-enzyme CD73, were enriched in TFH cells compared with TH 1 cells, and phenotypic analysis confirmed expression of CD73 on TFH cells. As there is now considerable interest in developing vaccines that would induce optimal TFH cell responses, the identification of two novel cell surface markers should be useful in characterization and identification of TFH cells following vaccination and infection. This article is protected by copyright. All rights reserved.

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