# Regulatory T cell therapy in lung transplantation: bridging the gap from bench to bedside

**Authors:** Qianwei Li, Guorui Li, Jinteng Feng, Guangjian Zhang

PMC · DOI: 10.3389/fimmu.2025.1654561 · 2025-10-22

## TL;DR

Regulatory T cells could improve lung transplant outcomes by modulating the immune system, but more research is needed to apply them effectively in this context.

## Contribution

This paper reviews how Treg therapy can be adapted for lung transplantation, focusing on immune modulation and clinical implementation strategies.

## Key findings

- Tregs can influence immune responses in lung allografts and affect rejection and tolerance.
- Preclinical and clinical data suggest Treg therapy is safe and may reduce the need for conventional immunosuppression.
- Key factors like administration timing and integration with current protocols are critical for successful clinical use.

## Abstract

Lung transplant recipients face significantly poorer outcomes compared to other solid organ transplants, with median survival rates substantially lower despite current immunosuppressive regimens. Regulatory T cell (Treg) therapy has emerged as a promising approach for immune modulation, though its successful application in lung transplantation requires understanding of the unique pulmonary immune environment. This review examines how Tregs mediate immune responses in lung allografts and their role in rejection and tolerance pathways. We evaluate emerging evidence from preclinical studies of Treg therapy in lung transplantation, complemented by clinical experience from kidney and liver transplant trials that demonstrate safety and potential for reducing conventional immunosuppression. The analysis addresses key considerations for clinical implementation, including therapeutic strategies, timing of administration, and integration with existing protocols. This framework aims to guide the development of Treg-based therapies specifically tailored for lung transplant recipients.

## Full-text entities

- **Genes:** CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, FOXP3 (forkhead box P3) [NCBI Gene 50943] {aka AIID, DIETER, IPEX, JM2, PIDX, XPID}, Foxp3 (forkhead box P3) [NCBI Gene 20371] {aka JM2, scurfin, sf}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, CXADRP1 (CXADR pseudogene 1) [NCBI Gene 653108] {aka CAR, CXADRP}, IDO1 (indoleamine 2,3-dioxygenase 1) [NCBI Gene 3620] {aka IDO, IDO-1, INDO}, ADO (2-aminoethanethiol dioxygenase) [NCBI Gene 84890] {aka C10orf22}, CD80 (CD80 molecule) [NCBI Gene 941] {aka B7, B7-1, B7.1, BB1, CD28LG, CD28LG1}, Il2 (interleukin 2) [NCBI Gene 16183] {aka Il-2}, IL2RA (interleukin 2 receptor subunit alpha) [NCBI Gene 3559] {aka CD25, IDDM10, IL2R, IMD41, TCGFR, p55}, GZMB (granzyme B) [NCBI Gene 3002] {aka C11, CCPI, CGL-1, CGL1, CSP-B, CSPB}, Ccr4 (C-C motif chemokine receptor 4) [NCBI Gene 12773] {aka C-C CKR-4, CHEMR1, Cmkbr4, LESTR, Sdf1r}, HLA-A (major histocompatibility complex, class I, A) [NCBI Gene 3105] {aka HLAA}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, Cd274 (CD274 antigen) [NCBI Gene 60533] {aka A530045L16Rik, B7h1, Pdcd1l1, Pdcd1lg1, Pdl1}, CD86 (CD86 molecule) [NCBI Gene 942] {aka B7-2, B7.2, B70, BU63, CD28LG2, CD86 v6}, NT5E (5'-nucleotidase ecto) [NCBI Gene 4907] {aka CALJA, CD73, E5NT, NT, NT5, NTE}, CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493] {aka ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, ENTPD1 (ectonucleoside triphosphate diphosphohydrolase 1) [NCBI Gene 953] {aka ATP-DPH, ATPDase, CD39, NTPDase-1, SPG64}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, Il33 (interleukin 33) [NCBI Gene 77125] {aka 9230117N10Rik, Il-33, Il1f11, NF-HEV}, TIGIT (T cell immunoreceptor with Ig and ITIM domains) [NCBI Gene 201633] {aka VSIG9, VSTM3, WUCAM}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, HLA-C (major histocompatibility complex, class I, C) [NCBI Gene 3107] {aka D6S204, HLA-JY3, HLAC, HLC-C, MHC, PSORS1}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, IL2RB (interleukin 2 receptor subunit beta) [NCBI Gene 3560] {aka CD122, IL15RB, IMD63, P70-75}, Cxcl13 (C-X-C motif chemokine ligand 13) [NCBI Gene 55985] {aka 4631412M08Rik, ANGIE2, Angie, BCA-1, BLC, BLR1L}, Cxcr5 (C-X-C motif chemokine receptor 5) [NCBI Gene 12145] {aka Blr1, CXC-R5, CXCR-5, Gpcr6, MDR15}, Itgax (integrin alpha X) [NCBI Gene 16411] {aka Cd11c, Cr4, N418}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, CD28 (CD28 molecule) [NCBI Gene 940] {aka IMD123, Tp44}
- **Diseases:** leukopenia (MESH:D007970), autoimmune pathologies (MESH:D001327), BOS (MESH:D000092122), ACR (MESH:D000208), RAS (MESH:D002313), inflammation (MESH:D007249), fibrosis (MESH:D005355), AMR (MESH:D020274), infection (MESH:D007239), malignancy (MESH:D009369), hepatorenal toxicity (MESH:D006530), EVLP (MESH:C536830), cystic fibrosis (MESH:D003550), gastrointestinal side effects (MESH:D064420), edema (MESH:D004487)
- **Chemicals:** ATP (MESH:D000255), Methylprednisolone (MESH:D008775), Prednisone (MESH:D011241), tryptophan (MESH:D014364), CTX (MESH:D003520), MMF (MESH:D009173), Chimeric antigen (-), Adenosine (MESH:D000241), Prednisolone (MESH:D011239), Tacrolimus (MESH:D016559), Triphosphate (MESH:C005692), alemtuzumab (MESH:D000074323), basiliximab (MESH:D000077552), Sirolimus (MESH:D020123)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12586102/full.md

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Source: https://tomesphere.com/paper/PMC12586102