Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
CD8+ T-cell selection, function, and death in the primary immune response in vivo
Margaret F.C. Callan, … , Chris Hatton, Andrew J. McMichael
Margaret F.C. Callan, … , Chris Hatton, Andrew J. McMichael
Published November 15, 2000
Citation Information: J Clin Invest. 2000;106(10):1251-1261. https://doi.org/10.1172/JCI10590.
View: Text | PDF
Article Article has an altmetric score of 6

CD8+ T-cell selection, function, and death in the primary immune response in vivo

  • Text
  • PDF
Abstract

The primary immune response to Epstein Barr virus (EBV) is characterized by striking proliferation of EBV-specific CD8+ T cells. In this study we have investigated the clonal composition and functional properties of the cells mediating this primary response and have analyzed the mechanisms that control the downregulation of the primary response and the selection of memory cells. We show that massively expanded T-cell clones often dominate the primary antigen-specific T-cell response. Despite the enormous extent of expansion, the virus-specific T cells express high levels of intracellular perforin and are potently cytotoxic. They are, however, functionally heterogeneous in their ability to secrete proinflammatory cytokines, with subpopulations of the antigen-specific T cells being hyporesponsive. The primary response is closely regulated, and the majority of cells are programmed to die via a cytokine-rescuable pathway, leaving only small populations of memory T cells surviving. Comparison of the clonal composition of primary and memory responses in vivo shows that the clones that dominate the primary response are relatively heavily culled during the downregulation of the primary response and the establishment of T-cell memory.

Authors

Margaret F.C. Callan, Chrysoula Fazou, Hongbing Yang, Tim Rostron, Kathryn Poon, Chris Hatton, Andrew J. McMichael

×

Figure 1

Options: View larger image (or click on image) Download as PowerPoint
BV7S1 use by HLA-B8–restricted RAKFKQLL-specific T cells in patient NS21...
BV7S1 use by HLA-B8–restricted RAKFKQLL-specific T cells in patient NS21 during the primary response to EBV. PBMCs taken from patient NS21 during primary EBV infection were stained with TCR V region–specific mAb’s, with an anti-CD8 mAb, and with the B8/RAKFKQLL tetrameric complex. (a) Twenty-eight percent of the CD8+ T cells react with the B8/RAKFKQLL tetrameric complex; (b) 18% of CD8+ T cells express the TCR BV7S1 chain; (c) 57% of B8/RAKFKQLL tetramer–reactive T cells express BV7S1. (d) The overall CD8+ TCR repertoire of patient NS21 (filled bars) is distorted with an expanded population of CD8+ T cells expressing BV7S1. The mean TCR repertoire of a panel of 21 young control individuals is shown (open bars) for comparison.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Referenced in 5 patents
42 readers on Mendeley
See more details