Identification of novel markers for mouse CD4+ T follicular helper cells |
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Authors: | Smita S Iyer Donald R Latner Michael J Zilliox Megan McCausland Rama S Akondy Pablo Penaloza‐MacMaster Jeffrey Scott Hale Lilin Ye Ata‐Ur‐Rasheed Mohammed Tomoyuki Yamaguchi Shimon Sakaguchi Rama R Amara Rafi Ahmed |
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Institution: | 1. Emory Vaccine Center, Emory University School of Medicine, , Atlanta, GA, USA;2. Department of Microbiology and Immunology, Emory University School of Medicine, , Atlanta, GA, USA;3. Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, , Atlanta, GA, USA;4. Loyola University Center for Biomedical Informatics, Stritch School of Medicine, Loyola University Chicago, , Maywood, IL, USA;5. Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, , Boston, MA, USA;6. Department of Immunology, Third Military Medical University, , Chongqing, China;7. Immunology Frontier Research Center, Osaka University, , Osaka, Japan |
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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 FR4hi versus FR4lo 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. |
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Keywords: | B cells CD4+ T cells CD73 Folate R 4 Viral infection |
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