Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • 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
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Immune Environment in Glioblastoma (Feb 2023)
    • Korsmeyer Award 25th Anniversary Collection (Jan 2023)
    • Aging (Jul 2022)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • Circadian Rhythm (Oct 2021)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Research letters
    • Letters to the editor
    • Editor's notes
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Research letters
  • Letters to the editor
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Aging promotes acquisition of naive-like CD8+ memory T cell traits and enhanced functionalities
Jens Eberlein, … , Eric T. Clambey, Dirk Homann
Jens Eberlein, … , Eric T. Clambey, Dirk Homann
Published September 12, 2016
Citation Information: J Clin Invest. 2016;126(10):3942-3960. https://doi.org/10.1172/JCI88546.
View: Text | PDF
Research Article Immunology

Aging promotes acquisition of naive-like CD8+ memory T cell traits and enhanced functionalities

  • Text
  • PDF
Abstract

Protective T cell memory is an acquired trait that is contingent upon the preservation of its constituents and therefore vulnerable to the potentially deleterious effects of organismal aging. Here, however, we have found that long-term T cell memory in a natural murine host-pathogen system can substantially improve over time. Comprehensive molecular, phenotypic, and functional profiling of aging antiviral CD8+ memory T cells (CD8+ TM) revealed a pervasive remodeling process that promotes the gradual acquisition of distinct molecular signatures, of increasingly homogeneous phenotypes, and of diversified functionalities that combine to confer a CD8+ TM–autonomous capacity for enhanced recall responses and immune protection. Notably, the process of CD8+ TM aging is characterized by a progressive harmonization of memory and naive T cell traits, is broadly amenable to experimental acceleration or retardation, and serves as a constitutional component for the “rebound model” of memory T cell maturation. By casting CD8+ TM populations within the temporal framework of their slowly evolving properties, this model establishes a simple ontogenetic perspective on the principal organization of CD8+ T cell memory that may directly inform the development of improved diagnostic, prophylactic, and therapeutic modalities.

Authors

Jens Eberlein, Bennett Davenport, Tom Nguyen, Francisco Victorino, Kelsey Haist, Kevin Jhun, Anis Karimpour-Fard, Lawrence Hunter, Ross Kedl, Eric T. Clambey, Dirk Homann

×

Figure 8

Accelerating the maturation process of CD8+ TM: p14-titration chimeras.

Options: View larger image (or click on image) Download as PowerPoint
Accelerating the maturation process of CD8+ TM: p14-titration chimeras.
...
(A) Chimeras were constructed with graded p14+ TN numbers (2 × 102 to 2 × 105; color legend in panel B), and p14+ TE expansions were quantified in the MedLNs on days 3–4 (connected data points, respectively). (B) Kinetics of p14+ TE expansion/contraction and p14+ TM development in blood (5 combined experiments; n = 3–6); data for day 0 indicate p14+ TN retrieved in the absence of infection, and vertical colored lines indicate respective p14+ TE peak expansions. (C) Serum IFN-γ as a function of p14+ TN input number. (D) Absolute numbers of transferred p14+ TN (day 0), TE (day 8) and TM (day 109) in spleen; values indicate fold difference between p14+ TN and TM cellularity. (E) CD127 and CX3CR1 expression by splenic p14+ TE/M recovered from respective chimeras on days 8, 44, and 109. (F) Kinetics of phenotypic p14+ TE/M differentiation as function of p14+ TN precursor frequency. Analyses of splenic p14+ TE (day 8) and TM (days 44 and 109) were conducted as above; data points from p14+ TE/M analyzed at the same time point are connected by a line, and statistics compare p142e2 vs. p142e3-p142e5 chimeras. For comparative purposes, the graded background shading demarcates the spread of respective marker expression from young (Y, light) to old (O, dark) DbNP396+CD8+ TM in B6 mice (Figure 4 and Supplemental Figures 5–14). (G) Summary of preceding analyses comprising 48 markers categorized according to similarity between p14+ TM from young p142e5 chimeras (~7 weeks) and old DbNP396+CD8+ TM (≥80 weeks). (H) AT/rechallenge experiments were performed with 2 × 103 p14+ TM purified from respective p14-titration chimeras infected ~7 weeks earlier, AT, LCMV Armstrong challenge and quantification of II° p14+ TE expansions 8 days later (n = 3; representative of 3 similar experiments). *P < 0.05, **P < 0.01, and ***P < 0.001 by 1-way ANOVA or Student’s t test.

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts