Evidence map›Paper›PMID 40707326›Full record

ReviewTrends in immunology2025

Cell-intrinsic CD4 T cell tolerance: a new frontier in therapy?

Alexandra Cassano, Domenic Abbondanza, Anita S Chong, Maria-Luisa Alegre

Abstract readReview
In one paragraph

Review in Trends in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Alexandra CassanoDepartment of Medicine, University of Chicago, Chicago, IL, USA.
Domenic AbbondanzaDepartment of Medicine, University of Chicago, Chicago, IL, USA.
Anita S ChongDepartment of Surgery, University of Chicago, Chicago, IL, USA.
Maria-Luisa AlegreDepartment of Medicine, University of Chicago, Chicago, IL, USA. Electronic address: malegre@uchicago.edu.

Funding

T cell mechanisms that distinguish robust tolerance from metastable allograft acceptance and failed tolerance (Project 2)P01AI097113 · NIAID · UNIVERSITY OF CHICAGO · PI Maria-Luisa Alegre, Anita S Chong · 2012 to 2026
$23.8M
MULTIDISCIPLINARY CARDIAC SCIENCEST32HL007381 · NHLBI · UNIVERSITY OF CHICAGO · PI JEANNE M DECARA, Yoav Gilad · 1985 to 2026
$12.5M
INTERDISCIPLINARY TRAINING PROGRAM IN IMMUNOLOGYT32AI007090 · NIAID · UNIVERSITY OF CHICAGO · PI Peter Aidan Savage · 1985 to 2026
$11.7M
Role of Tregs in the acquisition and maintenance of Tconv anergy in transplantation toleranceR01AI194499 · NIAID · UNIVERSITY OF CHICAGO · PI Maria-Luisa Alegre · 2025 to 2026
$1.5M
American Heart Association-American Stroke Association 24PRE1192022NHLBI NIH HHS T32 HL007381NIAID NIH HHS P01 AI097113NIAID NIH HHS R01 AI194499NIAID NIH HHS T32 AI007090
6 · The paper itself

Abstract

CD4 T cell tolerance is essential for immune homeostasis but its mechanisms remain unclear. Although regulatory T cells (Tregs) mediate T cell-extrinsic tolerance, this review emphasizes the CD4 T cell-intrinsic pathways - anergy and exhaustion - that are triggered by suboptimal or persistent antigen stimulation. These states share transcriptional and epigenomic features across contexts such as cancer, pregnancy, and transplantation. Instead of being distinct, they form a spectrum of tolerance with potential for therapeutic targeting. CD154 has re-emerged as a promising target, although memory T cell tolerization remains challenging. A deeper understanding of what sustains or reverses CD4 T cell tolerance is key to designing treatments that induce/maintain tolerance in autoimmunity and transplantation, or restore functionality in cancer and chronic infection.

Indexed as

CD4-Positive T-LymphocytesImmune ToleranceAnimalsCD40 LigandHumansNeoplasmsT-Lymphocytes, RegulatoryCD40 Ligandanergyanti-CD154CD4 T cellexhaustiontolerance

Identifiers

PMID40707326
PMCPMC12313179

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.