Fig. 5: HLA-engineered Tregs promote long-term protection of human skin transplants to a degree comparable to autologous Tregs. | Nature Communications

Fig. 5: HLA-engineered Tregs promote long-term protection of human skin transplants to a degree comparable to autologous Tregs.

From: HLA matching or CRISPR editing of HLA class I/II enables engraftment and effective function of allogeneic human regulatory T cell therapy in a humanized mouse transplantation model

Fig. 5

A Immunodeficient BALB/c Rag2−/− cγc−/− mice grafted with human skin received intraperitoneal human PBMCs (5 × 106, n = 5) alone, with Tregs autologous to the PBMC donor (1 × 106 Treg, n = 5), with Treg allogeneic to the PBMC donor (1 × 106 Treg, n = 5), or with allogeneic HLA class 2 KO and HLA-E KI Treg (1 × 106, n = 6). Grafts were monitored for macroscopic signs of rejection over the following 100 days. B Percentage of grafts without large active lesions is plotted over time post-adoptive transfer of cells. Statistical significance was assessed using log rank test for trend (χ2(1) = 4.089, p = 0.0432). C–E Immunodeficient BALB/c Rag2−/− cγc−/− mice grafted with human skin received intraperitoneal human PBMCs (5 × 106) either alone (n = 4) or with autologous (n = 4), allogeneic (n = 4), or H/C edited (n = 4) Tregs (1 × 106). Grafts were monitored for macroscopic signs of rejection and were harvested at 15 days following adoptive transfer. C Macroscopic graft rejection score at study end. Individual data points with median group values are plotted. Groupwise differences assessed with the Kruskal-Wallis test against the reference group of PBMC (H(3) = 13.28, p = <0.0001, ϵ2 = 0.86). Post-hoc groupwise two-tailed Dunn’s tests: (allo) Z = 1.3, p = 0.195, r = 0.32; (auto) Z = 2.40, p = 0.016, r = 0.60; (H/C): Z = 3.47, p = 0.0005, r = 0.87). D–G Spatial mapping of 427 transcripts across five skin grafts (one each from experimental groups treated with PBMC alone, autologous Treg, or allogeneic Treg, and two from the experimental group treated with H/C Treg) D Heatmap of z values for the top 25 differentially expressed genes within skin grafts at study end. E Number of cells expressing PTPRC in skin grafts. F Number of cells expressing CD8A in skin grafts. G CD8 and PTPRC expression across grafts by experimental group. Scale bars represent pixel values, where 1px represents 0.2125 μm. Panel A Created in BioRender. McCallion, O. (2025) https://BioRender.com/a0dop2t. Source data are provided as a Source data file.

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