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 ...
    • Pancreatic Cancer (Jul 2025)
    • 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)
    • 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
Reprogramming of antiviral T cells prevents inactivation and restores T cell activity during persistent viral infection
David G. Brooks, … , Dorian B. McGavern, Michael B.A. Oldstone
David G. Brooks, … , Dorian B. McGavern, Michael B.A. Oldstone
Published June 1, 2006
Citation Information: J Clin Invest. 2006;116(6):1675-1685. https://doi.org/10.1172/JCI26856.
View: Text | PDF
Research Article Virology

Reprogramming of antiviral T cells prevents inactivation and restores T cell activity during persistent viral infection

  • Text
  • PDF
Abstract

Failure to clear persistent viral infections results from the early loss of T cell activity. A pertinent question is whether the immune response is programmed to fail or if nonresponsive T cells can specifically be fixed to eliminate infection. Although evidence indicates that T cell expansion is permanently programmed during the initial priming events, the mechanisms that determine the acquisition of T cell function are less clear. Herein we show that in contrast to expansion, the functional programming of T cell effector and memory responses in vivo in mice is not hardwired during priming but is alterable and responsive to continuous instruction from the antigenic environment. As a direct consequence, dysfunctional T cells can be functionally reactivated during persistent infection even after an initial program of inactivation has been instituted. We also show that early therapeutic reductions in viral replication facilitate the preservation of antiviral CD4+ T cell activity, enabling the long-term control of viral replication. Thus, dysfunctional antiviral T cells can regain activity, providing a basis for future therapeutic strategies to treat persistent viral infections.

Authors

David G. Brooks, Dorian B. McGavern, Michael B.A. Oldstone

×

Figure 5

Therapeutically decreasing viral loads prevents CD4+ T cell inactivation but only minimally preserves CD8+ T cell function.

Options: View larger image (or click on image) Download as PowerPoint

                  Therapeutically decreasing viral loads prevents CD4+
...
(A and B) The ability of SMARTA (A) and P14 (B) cells from untreated (gray bars) or ribavirin-treated (black bars) animals to produce IFN-γ, TNF-α, and IL-2 was determined on day 9 after infection with either LCMV Arm (left 2 bars in each graph) or Cl 13 (right 2 bars in each graph). The top graphs of each figure represent the frequency of cytokine-producing SMARTA (A) or P14 (B) cells. The bottom graphs of each figure represent the absolute number of SMARTA (A) or P14 (B) cells and the total number of cytokine-producing SMARTA or P14 cells. The bars represent the average ± SD of 4 mice in each group in 3 independent experiments. Note that the scales on the y axis differ for the cytokines analyzed. *Statistically significant increase (P < 0.05) between the untreated and ribavirin-treated animals; **P ≤ 0.01.

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

Sign up for email alerts