# The relativity of regulatory T cell suppression modes

**Authors:** Lu Bai, Vivek Choudhary, Yongqiang Feng

PMC · DOI: 10.3389/fimmu.2026.1771099 · Frontiers in Immunology · 2026-02-10

## TL;DR

This paper explores how regulatory T cells adjust their suppression abilities based on antigen levels and TCR signals.

## Contribution

The paper introduces a model where Treg suppression modes vary with antigen levels and TCR signal strength.

## Key findings

- Treg cells have diverse TCR repertoires against various antigens.
- Variations in TCR repertoire during Treg induction affect target coverage.
- Treg suppression modes are context-dependent and influenced by antigen levels.

## Abstract

Foxp3-expressing CD4 regulatory T (Treg) cells are essential for maintaining immune tolerance through antigen-specific and bystander suppression modes. They carry a diverse T-cell antigen receptor (TCR) repertoire against a broad spectrum of antigens. The TCR repertoire acquired during Treg induction exhibits significant variations across antigens, leading to uncertainty in target coverage and representation. Accumulating reports indicate a remarkable complexity in the functional modes of Treg cells under various immunological contexts, presenting significant challenges for further investigation. In this article, we propose that the relative significance and capabilities of Treg suppression modes shift according to the levels of specific antigens and the resulting TCR signal strength. Testing the applicability of this model and identifying its modifiers would offer valuable insights for basic research and translational applications.

## Linked entities

- **Genes:** FOXP3 (forkhead box P3) [NCBI Gene 50943]
- **Proteins:** Tcr (Third chromosome alpha methyl dopa-resistant)

## Full-text entities

- **Genes:** Il2 (interleukin 2) [NCBI Gene 16183] {aka Il-2}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, Entpd1 (ectonucleoside triphosphate diphosphohydrolase 1) [NCBI Gene 12495] {aka 2610206B08Rik, ATP-DPH, Cd39, E130009M23Rik, NTPDase-1}, Foxp3 (forkhead box P3) [NCBI Gene 20371] {aka JM2, scurfin, sf}, Rr383 (regulatory region 383) [NCBI Gene 64821] {aka CNS-1, Cigs1, Cns1, DCR, HSS1, HSS2}, Ctla4 (cytotoxic T-lymphocyte-associated protein 4) [NCBI Gene 12477] {aka Cd152, Ctla-4, Ly-56}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, Il33 (interleukin 33) [NCBI Gene 77125] {aka 9230117N10Rik, Il-33, Il1f11, NF-HEV}, Aire (autoimmune regulator) [NCBI Gene 11634], Trp2 (tRNA proline 2) [NCBI Gene 104042] {aka Trp-2}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 21803] {aka TGF-beta1, TGFbeta1, Tgfb, Tgfb-1}, Il18 (interleukin 18) [NCBI Gene 16173] {aka Igif, Il-18}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, TRBV20OR9-2 (T cell receptor beta variable 20/OR9-2 (non-functional)) [NCBI Gene 6962] {aka CDR3, TCRBV20S2, TCRBV2O, TCRBV2S2O}, Il2ra (interleukin 2 receptor, alpha chain) [NCBI Gene 16184] {aka CD25, Il2r, Ly-43}, Cd80 (CD80 antigen) [NCBI Gene 12519] {aka B71, Cd28l, Ly-53, Ly53, MIC17, TSA1}, H3c7 (H3 clustered histone 7) [NCBI Gene 260423] {aka H3.2-221, H3c13, H3c14, H3c15, H3c2, H3c3}, Stat5a (signal transducer and activator of transcription 5A) [NCBI Gene 20850] {aka STAT5}, FOXP3 (forkhead box P3) [NCBI Gene 50943] {aka AIID, DIETER, IPEX, JM2, PIDX, XPID}, H2 (histocompatibility-2, MHC) [NCBI Gene 111364] {aka H-2, MHC-II}, Tcaf3 (TRPM8 channel-associated factor 3) [NCBI Gene 403088] {aka Eapa2, Fam115e}, Tnfrsf9 (tumor necrosis factor receptor superfamily, member 9) [NCBI Gene 21942] {aka 4-1BB, A930040I11Rik, CDw137, Cd137, ILA, Ly63}, Areg (amphiregulin) [NCBI Gene 11839] {aka AR, Mcub, Sdgf}, Cd86 (CD86 antigen) [NCBI Gene 12524] {aka B7, B7-2, B7.2, B70, CLS1, Cd28l2}, Trpc1 (transient receptor potential cation channel, subfamily C, member 1) [NCBI Gene 22063] {aka Mtrp1, Trp1, Trrp1}, Trav6-3 (T cell receptor alpha variable 6-3) [NCBI Gene 328483] {aka Gm13948, Gm193, Gm4, TCR}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Nt5e (5' nucleotidase, ecto) [NCBI Gene 23959] {aka 2210401F01Rik, 5'-NT, CD73, NT, Nt5, eNT}
- **Diseases:** autoimmune dysregulation (MESH:C580192), prostate (MESH:D011472), multiple sclerosis (MESH:D009103), autoimmune diabetes (MESH:D003922), experimental autoimmune encephalomyelitis (MESH:D004681), infection (MESH:D007239), immunological diseases (MESH:D007154), autoimmune (MESH:D001327), lung injury (MESH:D055370), cancer (MESH:D009369), autoimmune inflammation (MESH:D007249)
- **Chemicals:** LPS (MESH:D008070), ATP (MESH:D000255), retinoic acid (MESH:D014212), LLO190-201 (-), poly(I:C) (MESH:D011070), adenosine (MESH:D000241)
- **Species:** Listeria monocytogenes (species) [taxon 1639], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** MJ23 — Homo sapiens (Human), Primary cutaneous T-cell non-Hodgkin lymphoma, Cancer cell line (CVCL_1414)

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12929528/full.md

## References

91 references — full list in the complete paper: https://tomesphere.com/paper/PMC12929528/full.md

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Source: https://tomesphere.com/paper/PMC12929528