Distinct memory CD4+ T cells with commitment to T follicular helper- and T helper 1-cell lineages are generated after acute viral infection

• Type of Material: Article
• Authors: J. Scott Hale, Emory University; Benjamin Alan Youngblood, Emory University; Donald R. Latner, Emory University; Mohammed Ata Ur Rasheed, Emory University; Lilin Ye, Emory University; Rama Akondy, Emory University; Tuoqi Wu, Emory University; Smita Iyer, Emory University; Rafi Ahmed, Emory University
• Language: English
• Date: 2013-04-18
• Publisher: Elsevier (Cell Press)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.immuni.2013.02.020
• Title of Journal or Parent Work: Immunity
• ISSN: 1074-7613
• Volume: 38
• Issue: 4
• Start Page: 805
• End Page: 817
• Grant/Funding Information: This work was supported by the National Institutes of Health (NIH) grant P01 A1080192 (to R.A.), grant RO1 AI030048 (to R.A.), Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery UM1AI100663 (to R.A), the American Cancer Society (ACS) postdoctoral fellowship PF-09-134-01-MPC (to B.A.Y.), and the National Institute of Allergy and Infectious Diseases Training Grant T32AI074492 and F32 A1096709-01A1 (to J.S.H.).
• Research Categories: Biology, Virology; Health Sciences, Immunology; Biology, Microbiology

Abstract

Summary CD4+ T follicular helper (Tfh) cells provide the required signals to B cells for germinal center reactions that are necessary for long-lived antibody responses. However, it remains unclear whether there are CD4+ memory T cells committed to the Tfh cell lineage after antigen clearance. Using adoptive transfer of antigen-specific memory CD4+ T cell subpopulations in the LCMV infection model, we found that there are distinct memory CD4+ T cell populations with commitment to either Tfh- or Th1-cell lineages. Our conclusions are based on gene expression profiles, epigenetic studies, and phenotypic and functional analyses. Our findings indicate that CD4+ memory T cells “remember” their previous effector lineage after antigen clearance, being poised to reacquire their lineage-specific effector functions upon antigen reencounter. These findings have important implications for rational vaccine design, where improving the generation and engagement of memory Tfh cells could be used to enhance vaccine-induced protective immunity.