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Author Notes:

Correspondence to: Cheng Zhu, Coulter Department of Biomedical Engineering 313 Ferst Street, U. A. Whitaker Building, Georgia Institute of Technology, Atlanta, Georgia 30332-0535, USA, Phone: 1-404-894-3269; cheng.zhu@bme.gatech.edu & Arash Grakoui (Lead Contact), Emory Vaccine Center 954 Gatewood Rd, Room 3020, Atlanta, GA 30329, USA, Phone: 1-404-727-7217; arash.grakoui@emory.edu.

Y.S. and P.J. performed the experiments; M.S. performed the transcriptional profiling analysis; Y.S., P.J., M.S., C.Z. and A.G. conceived and designed the experiments, interpreted the data, and wrote the manuscript.

We thank Drs. Rafi Ahmed, David Weiss, Brian Evavold, and Christopher Walker for helpful discussions.

We would like to thank Drs. David Masopust and Jacob Kohlmeier for helping us to establish and adapt the intravascular staining procedure and Larissa Doudy for technical support.

Subjects:

Research Funding:

We acknowledge the NIH Tetramer Core Facility (contract HHSN272201300006C) for provision of tetramers.

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).

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.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Immunology
  • LYMPHOCYTIC CHORIOMENINGITIS VIRUS
  • TGF-BETA
  • TRANSCRIPTIONAL CONTROL
  • VIRAL-INFECTION
  • EFFECTOR
  • KINETICS
  • TCR
  • DIFFERENTIATION
  • ACTIVATION
  • SELECTION

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

Tools:

Journal Title:

Immunity

Volume:

Volume 45, Number 5

Publisher:

, Pages 988-998

Type of Work:

Article | Post-print: After Peer Review

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.

Copyright information:

© 2016 Elsevier Inc.

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