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Fig. 2 | Inflammation and Regeneration

Fig. 2

From: Evaluation of immunosuppression protocols for MHC-matched allogeneic iPS cell-based transplantation using a mouse skin transplantation model

Fig. 2

Blockade of leukocyte costimulatory molecules permits long-term engraftment of mouse skin grafts from MHC-matched allogeneic donors. (A) CB-based immunoregulation protocol. Immunosuppression was performed by using a protocol of administrating a combination of anti-CD40L mAb and CTLA4-Ig daily (CB) with or without rapamycin on every 3 days from POD 1 (CB + rapa). (B) Skin graft survival under immunosuppression with CB (n = 9, C3129F1; n = 9, BALB/c; n = 9, C57BL/6; n = 9, CBA/N). (C) Skin graft survival under immunosuppression with CB + rapa (n = 9, C3129F1; n = 8, BALB/c; n = 9, C57BL/6; n = 9, CBA/N). (D) Macroscopic observation (upper panels) and hematoxylin and eosin stained section (lower panels) of autologous (C3129F1), CBA/N, and C57BL/6 skin grafts on day 100. Scale bars: 100 μm. (E) Immunohistochemical staining for CD3 of C57BL/6 skin grafts harvested from CB or CB + rapa treated groups on 100 days post-transplantation. Upper and lower panels represent CD3 specific staining and isotype control stained section, respectively. Scale bars: 100 μm. (F) Recipient T cell response in MHC-matched but minor antigen-mismatched skin transplantation. The T cell proliferation rates in each treatment group were normalized to that of C3129F1 mice stimulated with autologous irradiated splenocytes. Error bars indicate standard error of technical triplicates. Similar results were obtained in two independent experiments. *p < 0.05, **p < 0.01 (Tukey’s HSD test). (G) De novo anti-donor antibody production in the recipients. Error bars indicate standard error of biological replicates (n = 8, naive; n = 4, non-treatment; n = 9, CB; n = 9, CB + rapa). tx, transplantation; mAb, monoclonal antibody; CB, co-stimulatory molecule blocking; rapa, rapamycin; POD, post-operative day

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