【正文】 Zhao Y, et al Nature Medicine 1996 Zhao Y, et al, J of Immunol 1997, Zhao Y, et al, J of Immunol 1998 Zhao Y, et al, Xenotransplantation 1998 Zhao Y, et al, Transplantation 2022 Zhao Y, et al, Transplantation 2022 Zhao Y, et al, Transplantation 2022 Zhao Y, et al, Cel Mol Biol 2022 在異種豬胸腺中成熟的 T細(xì)胞具有抗腫瘤作用嗎？ 12 wks 5x105 B16 cells 小鼠死亡率 胎豬胸腺 C57小鼠來(lái)源的黑色素瘤 B16抗原免疫 12 days 脾細(xì)胞 裸鼠 (C57 NUDE,T細(xì)胞缺乏 ) Tumor adoptive immunotherapy by hosttype antitumor T cells maturing in xenogeneic pig thymus Days postB16 injection % survival 0 20 40 60 80 100 0 20 40 60 80 100 Control (5) Splenocytes from immunized FP THY nude mice (6) P 腫瘤治療組 Zhao Y, et al. J of immunotherapy 2022. 12 wks Athymic B6 mice (nude, immunodeficiency) 1x105 B16 cells 實(shí)體瘤大小 FP THY B16 immunization 12 days splenocytes Days postinjection of B16 cells Tumor size (mm) 0 2 4 6 8 10 12 14 0 5 10 15 20 *** ** * ** * ** ** *** Control (6) Splenocytes from immunized FP THYgrafted nude mice (7) Inhibition of B16 tumor growth by injection of host antitumor T cells maturing in pig thymus Zhao Y, et al. J of immunotherapy 2022. 腫瘤 /AIDS患者 人 T細(xì)胞免疫 重建的供體豬 骨髓細(xì)胞 人特異抗腫瘤 /HIV T細(xì)胞 腫瘤 /HIV抗原 腫瘤及 AIDS的過(guò)繼性免疫療法 調(diào)節(jié)性 CD4+CD25+T細(xì)胞在異種胸腺中可以進(jìn)行正常分化嗎 ? 胎豬胸腺 裸鼠 (NUDE,T細(xì)胞缺乏 ) Mouse Treg cells Number Phenotype function Experimental model 0 1 2 3 4 5 6 7 8 9 10 NP THYnude mice Control Balb/c mice % of CD4+ CD25+ cells in CD4+ cells 0 2 4 6 8 10 12 14 16 0 2 4 6 8 10 12 14 16 18 % of CD4+ CD25+ cells in CD4+ cells % of CD4+ CD25+ cells in CD4+ cells PBLs SPL LNs a c b NP THYnude mice Control Balb/c mice NP THYnude mice Control Balb/c mice B A Nude mice Balb/c mice NP THYnude mice CD25 CD4 The presence of mouse CD4+CD25+Treg cells in NP THYgrafted nude mice Sun ZY, Wang HJ, Sun LG, Zhao L, Yi HF, Li QH, Peng JX, and Zhao Y. American J of Transplantation 2022， 6： 110. A Cell number FOXP3 89% 91% NP THYnude mice Balb/c mice CD4+CD25+T cells CD4+CD25 T cells B C % of FOXP3+ cells/CD4+ CD25+ cells 0 10 20 30 40 50 60 70 80 90 100 NP THYnude mice Control Balb/c mice MFI of FOXP3+ T cells 0 10 20 30 40 50 60 NP THYnude mice Control Balb/c mice Normal expression of Foxp3 in CD4+CD25+Treg cells in NP THYgrafted nude mice Sun ZY, Wang HJ, Sun LG, Zhao L, Yi HF, Li QH, Peng JX, and Zhao Y. American J of Transplantation 2022， 6： 110. AlloMLR Response to OVA A B [3 H]Thymidine uptake (cpm x 103) 0 2 4 6 8 10 12 14 Treg cells from NP THYnude mice Treg cells from Balb/c mice * 0:1 1:1 1:2 1:4 1:8 *** *** ** ** Treg: T responder cells 0 5 10 15 20 25 30 0:1 1:1 1:2 1:4 1:8 1:16 1:32 [3 H]Thymidine uptake (cpm x 103) Treg: T responder cells *** *** *** ** *** *** * The function of Treg cells in NP THYgrafted nude mice Sun ZY, Wang HJ, Sun LG, Zhao L, Yi HF, Li QH, Peng JX, and Zhao Y. American J of Transplantation 2022， 6： 110. 10 12 14 16 18 20 22 24 26 28 1 2 3 4 5 6 7 8 9 10 11 Body weight (g) Weeks Treg cells from NP THYnude mice + Tresp cells (1:2) Tresp cells (CD4+CD25T cells) Treg cells from Balb/c mice + Tresp cells (1:2) Treg cells from Balb/c cells + Tresp cells (1:1) Treg cells from NP THYnude mice + Tresp cells (1:1) Control mice received no cells * * * * ** ** ** ** ** ** ** ** ** ** ** ** The function of Treg cells in NP THYgrafted nude mice Sun ZY, Wang HJ, Sun LG, Zhao L, Yi HF, Li QH, Peng JX, and Zhao Y. American J of Transplantation 2022， 6： 110. 人 T細(xì)胞可以在異種豬胸腺中可以進(jìn)行正常分化嗎 ? Phenotype and repopulation of T cell from grafts of FH Thy/Livgrafted SCID mice Zhang Baojun et al, unpublished data FH THY NP THY/FH LIV The levels of human CD4+ T cells in the peripheral blood of FH Thy/Livgrafted SCID mice AntihTCRFITC AntihCD8PE AntihCD4PE Zhang Baojun et al, unpublished data Exp Control Exp Control Tolerance to donor pig of human T cells maturing xenogeneic pig thymus Immune response Positive Immune response Negative immune response Immune tolerance Effector T cells Effector T cells Regulatory T cells Regulatory T cells Immune response Immune tolerance Graft rejection Graft survival Zhao Y. Medical Hypothesis 2022 Positive Immune responserejection Negative immune response Immune tolerance Immunisuppressive agents CsA, Rapa, antiCD4 mAb, irradiation ? Graft rejection Regulatory CD4+CD25+Foxp3+T cells Effector T cells Zhang LJ J Cell Phy 2022 Liu GW Immunology 2022 Yi HF Exp Rev of CLin Immunol 2022 A % of CD4+ CD25+ /CD4+ cells ** 0 5 10 15 20 25 30 B Control CsA Spleen LNs Total cell no of CD4+ CD25+ cells (X106) * 0 1 2 3 Control CsA Spleen LNs CsA significantly decreased the percentages of CD4+CD25+Treg cells in spleens Wang HJ, Zhao L, Sun ZY, Sun LG, and Zhao Y. Transplantation 2022. C ** * * ** * 0 25 50 75 100 125 150 3 HTdR uptake (cpm103 ) 0 1 2 4 0 5 10 15 20 25 0 50 100 150 200 3 HTdR