Identification of novel markers for mouse CD4(+) T follicular helper cells Journal Article

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Authors: Iyer, S. S.; Latner, D. R.; Zilliox, M. J.; McCausland, M.; Akondy, R. S.; Penaloza-MacMaster, P.; Hale, J. S.; Ye, L.; Mohammed, A. U.; Yamaguchi, T.; Sakaguchi, S.; Amara, R. R.; Ahmed, R.
Article Title: Identification of novel markers for mouse CD4(+) T follicular helper cells
Abstract: 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 R CXCR5, and TFH cells are typically identified by co-expression of CXCR5 together with other markers such as PD-1, ICOS, and Bcl-6. Herein, we report high-level expression of the nutrient transporter folate R 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) Ag-specific CD4(+) effector T cells revealed a molecular signature consistent with TFH and TH1 subsets, respectively. Interestingly, genes involved in the purine metabolic pathway, including the ecto-enzyme CD73, were enriched in TFH cells compared with TH1 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.
Journal Title: European journal of immunology
Volume: 43
Issue: 12
ISSN: 1521-4141; 0014-2980
Publisher: WILEY-VCH Verlag GmbH Co. KGaA, Weinheim  
Journal Place: Germany
Date Published: 2013
Start Page: 3219
End Page: 3232
Language: eng
DOI/URL:

10.1002/eji.201343469
Notes: LR: 20140416; CI: (c) 2013; GR: P30 CA68485/CA/NCI NIH HHS/United States; GR: P30 DK58404/DK/NIDDK NIH HHS/United States; GR: P30 EY08126/EY/NEI NIH HHS/United States; GR: P51 OD011132/OD/NIH HHS/United States; GR: R01 A1030048/PHS HHS/United States; GR: R01 AI030048/AI/NIAID NIH HHS/United States; GR: U19 AI057266/AI/NIAID NIH HHS/United States; GR: UM1 AI100663/AI/NIAID NIH HHS/United States; JID: 1273201; 0 (Bcl6 protein, mouse); 0 (Blr1 protein, mouse); 0 (DNA-Binding Proteins); 0 (Icos protein, mouse); 0 (Inducible T-Cell Co-Stimulator Protein); 0 (Pdcd1 protein, mouse); 0 (Programmed Cell Death 1 Receptor); 0 (Receptors, CXCR5); 0 (Receptors, Cell Surface); 0 (folate receptor 4, mouse); EC 3.1.3.5 (5'-Nucleotidase); NIHMS527153; OID: NLM: NIHMS527153 [Available on 12/01/14]; OID: NLM: PMC3947211 [Available on 12/01/14]; OTO: NOTNLM; PMCR: 2014/12/01 00:00; 2013/02/21 [received]; 2013/07/29 [revised]; 2013/09/09 [accepted]; 2013/10/14 [aheadofprint]; ppublish