Long-term skin resident memory T cells in human graft-versus-host disease

Key Highlights

• TRM persistence: Skin-resident memory T cells (TRM) survive radiochemotherapy and remain detectable up to 10 years after stem cell transplantation.
• Clonal expansion: Resistant TRM proliferate locally, express Ki-67, and expand clonally despite donor cell replacement in blood.
• GVHD involvement: Patients who later developed GVHD already had elevated TRM at transplantation; during GVHD, TRM showed enhanced proliferation and cytokine production.
• Donor vs. host dynamics: Host TRM coexist with donor T cells in skin lesions, displaying strong patient-to-patient variability in dominance.
• Regulatory T cells: In GVHD, most regulatory T cells were donor-derived, highlighting limited host Treg contribution.

Webinar Summary

Title: Long-term Skin-Resident Memory T Cells in Graft-versus-Host Disease
Presenter: Johanna Strobel, Medical University of Vienna
Associated Publication:
Strobl J, et al. Long-term skin-resident memory T cells proliferate in situ and are involved in human graft-versus-host disease.
Sci Transl Med. 2020 Nov 18;12(570) https://doi.org/10.1126/scitranslmed.abb7028

This webinar presented novel findings on the role of tissue-resident memory T cells (TRM) in human graft-versus-host disease (GVHD). Traditionally, pre-transplant radiochemotherapy is thought to eradicate host immune cells; however, this study revealed that TRM in skin resist elimination and persist long-term.

Study Design & Methods

• Patients sampled before and after transplantation (blood + skin).
• Analysis performed with TissueFAXS and StrataQuest (including a new chimerism workflow).
• Sex-mismatched transplants enabled tracking of donor vs. host origin via immunostaining + XY FISH.

Findings

• Persistence: While blood T cells were almost completely replaced by donor-derived cells, ~50–60% of skin T cells remained host-derived even a decade post-transplant.
• Clonality: TRM clones persisted, expanded, and expressed proliferation marker Ki-67 despite chemotherapy.
• GVHD Link: Elevated TRM were detectable before GVHD onset, and in active GVHD lesions, TRM showed strong proliferation and cytokine production (Granzyme B, IFN-γ).
• Donor–Host Balance: Immune infiltrates in GVHD lesions varied — some dominated by donor cells, others a mix of donor and host TRM.
• Regulatory T Cells: Tregs were predominantly donor-derived, suggesting different dynamics compared to effector TRM.

Conclusion

TRM are radio-resistant, long-lived, and clonally expanding populations that actively contribute to GVHD pathogenesis. Their ability to proliferate, produce cytokines, and persist long-term positions them as central players in post-transplant immune dynamics, with potential as therapeutic targets and biomarkers.