# T cell-mediated immune responses in xenotransplantation: mechanisms and therapeutic strategies

**Authors:** Ziyue Wang, Guomu Liu

PMC · DOI: 10.3389/fimmu.2026.1767840 · Frontiers in Immunology · 2026-02-23

## TL;DR

This paper reviews how T cells contribute to rejection in xenotransplantation and explores strategies to improve graft survival.

## Contribution

The paper provides a focused review on T cell-mediated immune responses and potential therapeutic strategies in xenotransplantation.

## Key findings

- T cells are central to cell-mediated rejection in xenotransplantation.
- Strategies to induce immune tolerance are critical for clinical success.
- Gene-editing has reduced hyperacute rejection but not T cell-mediated rejection.

## Abstract

Xenotransplantation has emerged as a promising approach to alleviate the shortage of donor organs. While advances in porcine gene-editing technologies have largely overcome hyperacute rejection, the persistent challenge of T cell- and antibody-mediated rejection reactions continues to impede the long-term survival and clinical translation of xenografts. T cells connect innate and adaptive immunity and are the main effector cells in cell-mediated rejection reactions. The antigen recognition, activation, and effector differentiation of T cells have a crucial impact on the clinical outcomes of xenotransplantation. This review focuses on the immune response process of T cells in xenotransplantation and discusses potential strategies for T cell-mediated rejection reactions. Future exploration of efficient and safe approaches for inducing immune tolerance will be a key direction for prolonging the survival of xenografts.

## Full-text entities

- **Genes:** HLA-C (major histocompatibility complex, class I, C) [NCBI Gene 3107] {aka D6S204, HLA-JY3, HLAC, HLC-C, MHC, PSORS1}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, IFNG (interferon gamma) [NCBI Gene 396991], SIRPA (signal regulatory protein alpha) [NCBI Gene 494566] {aka CD172, PTPNS1, swc3}, APC (APC regulator of WNT signaling pathway) [NCBI Gene 100517932] {aka APC1}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, HMOX1 (heme oxygenase 1) [NCBI Gene 445512] {aka HSP32}, CD47 (CD47 molecule) [NCBI Gene 397042] {aka CD47/IAP}, FASLG (Fas ligand) [NCBI Gene 356] {aka ALPS1B, APT1LG1, APTL, CD178, CD95-L, CD95L}, CD40 (CD40 molecule) [NCBI Gene 397395] {aka TNFRSF5}, CD2 (CD2 molecule) [NCBI Gene 914] {aka LFA-2, SRBC, T11}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, TFRC (transferrin receptor) [NCBI Gene 397062] {aka trfr}, GALT (galactose-1-phosphate uridylyltransferase) [NCBI Gene 100623908], IL10 (Interleukin 10 level) [NCBI Gene 103158318], IL6 (interleukin 6) [NCBI Gene 399500] {aka IL-6}, FOXP3 (forkhead box P3) [NCBI Gene 444998], IL1B (interleukin 1 beta) [NCBI Gene 397122] {aka IL1B1}, CCL5 (C-C motif chemokine ligand 5) [NCBI Gene 6352] {aka D17S136E, RANTES, SCYA5, SIS-delta, SISd, TCP228}, CD4 (CD4 molecule) [NCBI Gene 404704], CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 397286], CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, B4GALNT2 (beta-1,4-N-acetyl-galactosaminyltransferase 2 (SID blood group)) [NCBI Gene 100621328], CD80 (CD80 molecule) [NCBI Gene 941] {aka B7, B7-1, B7.1, BB1, CD28LG, CD28LG1}, ICAM1 (intercellular adhesion molecule 1) [NCBI Gene 3383] {aka BB2, CD54, P3.58}, ICOSLG (inducible T cell costimulator ligand) [NCBI Gene 23308] {aka B7-H2, B7H2, B7RP-1, B7RP1, B7h, CD275}, CD28 [NCBI Gene 100738615], CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CD80 (CD80 molecule) [NCBI Gene 397161] {aka B7-1}, CD40 (CD40 molecule) [NCBI Gene 958] {aka Bp50, CDW40, TNFRSF5, p50}, VCAM1 (vascular cell adhesion molecule 1) [NCBI Gene 7412] {aka CD106, INCAM-100}, FAS (Fas cell surface death receptor) [NCBI Gene 355] {aka ALPS1A, APO-1, APT1, CD95, FAS1, FASTM}, LAG3 (lymphocyte activating 3) [NCBI Gene 3902] {aka CD223}, CD3E (CD3 epsilon subunit of T-cell receptor complex) [NCBI Gene 397455] {aka CD3}, CD274 (CD274 molecule) [NCBI Gene 574058] {aka PDL1}, CD14 (CD14 molecule) [NCBI Gene 929], CD28 (CD28 molecule) [NCBI Gene 940] {aka IMD123, Tp44}, FASLG (Fas ligand) [NCBI Gene 396726] {aka CD95-L, FASL, TNFSF6}, B2M (beta-2-microglobulin) [NCBI Gene 397033], MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 100127359] {aka FRAP1}, CD86 (CD86 molecule) [NCBI Gene 942] {aka B7-2, B7.2, B70, BU63, CD28LG2, CD86 v6}, SLA (Src like adaptor) [NCBI Gene 6503] {aka SLA1, SLAP}, CXCL10 (C-X-C motif chemokine ligand 10) [NCBI Gene 3627] {aka C7, IFI10, INP10, IP-10, SCYB10, crg-2}, CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493] {aka ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4}, CIITA [NCBI Gene 100736732], IL2 (Interleukin 2 level) [NCBI Gene 101055066], IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, CD40LG (CD40 ligand) [NCBI Gene 959] {aka CD154, CD40L, HIGM1, IGM, IMD3, T-BAM}, CD86 (CD86 molecule) [NCBI Gene 397441], SLA (Src like adaptor) [NCBI Gene 100156099], CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, IL17A (interleukin 17A) [NCBI Gene 449530] {aka IL17}, TNF (tumor necrosis factor) [NCBI Gene 397086] {aka TNFSF2, TNFa}, CD27 (CD27 molecule) [NCBI Gene 100520023], ITGAL (integrin subunit alpha L) [NCBI Gene 3683] {aka CD11A, EV6, HNA-5, LFA-1, LFA1A}, GGTA1 (glycoprotein alpha-galactosyltransferase 1) [NCBI Gene 396733] {aka GGTA1P, alpha1,3GT}, SELE (selectin E) [NCBI Gene 6401] {aka CD62E, ELAM, ELAM1, ESEL, LECAM2, selectin-e}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, CMAH (cytidine monophospho-N-acetylneuraminic acid hydroxylase) [NCBI Gene 396918], SELL (selectin L) [NCBI Gene 6402] {aka CD62L, LAM1, LECAM1, LEU8, LNHR, LSEL}
- **Diseases:** graft-versus-host disease (MESH:D006086), inflammation (MESH:D007249), acute (MESH:D000208), brain-dead (MESH:D001926), infection (MESH:D007239), end-stage organ failure (MESH:D007676), cytotoxicity (MESH:D064420), vascular injury (MESH:D057772), amyotrophic lateral sclerosis (MESH:D000690), thrombosis (MESH:D013927), microvascular injury (MESH:D017566), immunodeficiency (MESH:D007153), XDRTCCs (MESH:D000275)
- **Chemicals:** rapamycin (MESH:D020123), Basiliximab (MESH:D000077552), carbohydrate (MESH:D002241), AT-1501 (-), tacrolimus (MESH:D016559)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Sus scrofa (pig, species) [taxon 9823], Macaca (macaque, genus) [taxon 9539], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Cercopithecidae (monkey, family) [taxon 9527], Macaca mulatta (rhesus macaque, species) [taxon 9544]
- **Cell lines:** hCD4 — Cricetulus griseus (Chinese hamster), Spontaneously immortalized cell line (CVCL_9Y69), pCD86 — Chlorocebus pygerythrus (Vervet monkey), Spontaneously immortalized cell line (CVCL_VG41)

## Full text

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## Figures

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## References

164 references — full list in the complete paper: https://tomesphere.com/paper/PMC12967941/full.md

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Source: https://tomesphere.com/paper/PMC12967941