Local Cellular and Cytokine Cues in the Spleen Regulate In Situ T Cell Receptor Affinity, Function, and Fate of CD8(+) T Cells

• Type of Material: Article
• Authors: Young-Jin Seo, Emory University; Prithiviraj Jothikumar, Georgia Institute of Technology; Mehul Suthar, Emory University; Cheng Zhu, Emory University; Arash Grakoui, Emory University
• Language: English
• Date: 2016-11-15
• Publisher: Elsevier (Cell Press)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 Elsevier Inc.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.immuni.2016.10.024
• Title of Journal or Parent Work: Immunity
• ISSN: 1074-7613
• Volume: 45
• Issue: 5
• Start Page: 988
• End Page: 998
• Grant/Funding Information: This project was supported by NIH grants U19AI083019 and R56AI110516 to M.S.S., NIH grants AI038282, GM096187, and R01AI124680 to C.Z., and ORIP-OD P51OD011132 (formerly NCRR P51RR000165) to the Yerkes National Primate Research Center and NIH grants R01AI070101, R01AI124680, R01AI126890, and R21AI118337 to A.G.; Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.; We also would like to thank Yerkes Nonhuman Primate Genomics Core and the Immunology and Flow Cytometry Core of the Center for AIDS Research at Emory University (P30AI050409).; We acknowledge the NIH Tetramer Core Facility (contract HHSN272201300006C) for provision of tetramers.
• Keywords: Life Sciences & Biomedicine; LYMPHOCYTIC CHORIOMENINGITIS VIRUS; EFFECTOR; TGF-BETA; Immunology; SELECTION; VIRAL-INFECTION; TRANSCRIPTIONAL CONTROL; TCR; ACTIVATION; Science & Technology; KINETICS; DIFFERENTIATION
• Research Categories: Health Sciences, General; Engineering, Biomedical

Abstract

T cells rapidly undergo contraction upon viral clearance, but how T cell function and fate are determined during this phase is unclear. During the contraction phase of an acute infection with lymphocytic choriomeningitis virus, we found that virus-specific CD8 + T cells within the splenic red pulp (RP) had higher two-dimensional (2D) effective affinity than those within the white pulp (WP). This increased antigen recognition of RP-derived CD8 + T cells correlated with more efficient target cell killing and improved control of viremia. FoxP3 + regulatory T cells and cytokine TGF-β limited the 2D-affinity in the WP during the contraction phase. Anatomical location drove gene expression patterns in CD8 + T cells that led to preferential differentiation of memory precursor WP T cells into long-term memory cells. These results highlight that intricate regulation of T cell function and fate is determined by anatomic compartmentalization during the early immune contraction phase.