Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Journal Club
  • Published:

Preprint watch

Progenitor exhausted T cells contribute to the formation of immunological memory

Nature Reviews Immunology volume 25, page 405 (2025)Cite this article

Subjects

Access through your institution
Buy or subscribe

Memory T cells arise after acute infection or vaccination and persist long term to rapidly protect against reinfection. By contrast, chronic infection results in the development of exhausted T (Tex) cells with epigenetic profiles that limit T cell proliferation and differentiation. Tex cells exhibit decreased accessibility of effector gene loci and increased accessibility of loci that encode immune checkpoint molecules (such as Pdcd1 and Lag3) and transcription factors associated with exhaustion (such as Tox and Batf). Given that Tex cells are a diverse collection of distinctive cell types, and previous studies that have characterized Tex cells have been conducted on aggregate populations rather than individual clones, it remains unclear whether there exists a subset of Tex cell clones that can generate functional memory responses.

In a recent preprint (not peer reviewed), Raposo et al. leverage recent advances in single-cell RNA and T cell receptor (TCR) sequencing to identify a subset of T cells with functional memory capabilities that arise after chronic infection with lymphocytic choriomeningitis virus (LCMV). In accordance with the published literature, they validate that most Tex cells have transcriptional and epigenetic profiles previously associated with exhaustion; however, they find that the subset termed chronic central memory T (cTcm) cells have transcriptional and epigenetic similarities to bona fide central memory T (Tcm) cells that are generated in the setting of acute infection. Furthermore, the authors validated that cTcm cells and Tcm cells are functionally similar as adoptive transfer of both populations could protect against LCMV rechallenge in mice that lack endogenous T cells.

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

Original article

Related article

Download references

Author information

Authors and Affiliations

  1. Preprint Club, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Annette Wu & Wen Jiang

Authors
  1. Annette Wu
    View author publications

    Search author on:PubMed Google Scholar

  2. Wen Jiang
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Annette Wu.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, A., Jiang, W. Progenitor exhausted T cells contribute to the formation of immunological memory. Nat Rev Immunol 25, 405 (2025). https://doi.org/10.1038/s41577-025-01182-1

Download citation

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41577-025-01182-1

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing