【正文】 86 99 .8 8UR 2. 90 2. 90 28 6. 24 26 8. 99 59 .0 0LL 19 .2 4 19 .2 4 8. 46 5. 59 14 .3 4LR 13 .5 4 13 .5 4 28 9. 45 27 6. 63 15 .7 4Fi l e: 0 60 51 7. 01 0 Gat e: No Gat eQua d % Gat ed % T ot al X M ea n X Geo M ea n Y M ea nUL 62 .9 7 62 .9 7 5. 89 4. 68 13 2. 55UR 5. 37 5. 37 31 6. 07 30 1. 59 55 .9 0LL 19 .1 3 19 .1 3 7. 16 5. 05 14 .5 1LR 12 .5 3 12 .5 3 29 5. 41 28 8. 01 20 .4 1Fi l e: 06 05 1 7. 00 1 Gat e: No Gat eGat ed Ev en ts: 10 0 00 T ot al Ev e nt s: 1 00 0 0Qua d % Gat ed % T ot al X M ea n X Geo M ea n Y M ea nUL 0. 51 0. 51 9. 77 6. 22 96 .3 4UR 0. 14 0. 14 34 6. 42 33 3. 98 72 .9 6LL 76 .7 3 76 .7 3 5. 23 3. 92 6. 55LR 22 .6 2 22 .6 2 36 4. 22 35 0. 70 8. 36Fi l e: 06 05 1 7. 00 2 Gat e: No Gat eQua d % Gat ed % T ot al X M ea n X Geo M ea n Y M nUL 56 .0 7 56 .0 7 5. 28 4. 23 12 1. 52UR 1. 99 1. 99 40 9. 73 38 7. 22 54 .0 1LL 22 .7 2 22 .7 2 6. 49 4. 29 11 .5 9LR 19 .2 2 19 .2 2 35 6. 68 34 4. 44 18 .2 2Fi l e: 06 05 1 7. 00 3 Gat e: No Gat eQua d % Gat ed % T ot al X M ea n X Geo M ea n Y M ea nUL 57 .9 0 57 .9 0 5. 56 4. 54 10 7. 63UR 1. 35 1. 35 36 9. 86 34 0. 02 58 .8 2LL 22 .1 0 22 .1 0 7. 09 4. 61 12 .0 4LR 18 .6 5 18 .6 5 35 4. 82 34 1. 99 14 .4 5Fi l e: 06 05 1 7. 00 4 Gat e: No Gat eQua d % Gat ed % T ot al X M ea n X Geo M ea n Y M ea nUL 48 .7 2 48 .7 2 5. 48 4. 45 10 1. 66UR 1. 18 1. 18 39 5. 16 36 2. 35 53 .7 0LL 27 .1 1 27 .1 1 6. 55 4. 29 11 .1 2LR 22 .9 9 22 .9 9 35 4. 74 34 2. 05 13 .2 3Fi l e: 06 05 1 7. 00 5 Gat e: No Gat eQua d % Gat ed % T ot al X M ea n X Geo M ea n Y M ea nUL 1. 13 1. 13 8. 33 5. 04 58 .8 0UR 0. 12 0. 12 25 5. 21 22 2. 33 71 .2 0LL 80 .5 1 80 .5 1 5. 55 4. 30 7. 11LR 18 .2 4 18 .2 4 31 0. 83 30 1. 14 6. 90Fi l e: 06 05 1 7. 00 6 Gat e: No Gat eQua d % Gat ed % T ot al X M ea n X Geo M ea n Y M ea nUL 61 .6 3 61 .6 3 5. 21 4. 27 11 1. 35UR 1. 87 1. 87 33 8. 07 32 4. 10 54 .9 1LL 19 .5 6 19 .5 6 7. 14 4. 92 11 .5 3LR 16 .9 4 16 .9 4 30 9. 55 30 1. 85 16 .8 1Fi l e: 06 05 1 7. 00 7 Gat e: No Gat eQua d % Gat ed % T ot al X M ea n X Geo M ea n Y M ea nUL 60 .4 4 60 .4 4 5. 18 4. 22 12 0. 04UR 2. 84 2. 84 34 0. 17 32 4. 63 61 .3 5LL 20 .0 8 20 .0 8 6. 78 4. 73 12 .4 0LR 16 .6 4 16 .6 4 30 7. 98 30 1. 28 17 .1 7Fi l e: 06 05 1 7. 00 8 Gat e: No Gat eQua d % Gat ed % T ot al X M ea n X Geo M ea n Y M ea nUL 60 .1 4 60 .1 4 5. 68 4. 76 10 4. 86UR 1. 88 1. 88 33 8. 78 31 8. 49 53 .1 7LL 20 .8 1 20 .8 1 7. 48 5. 30 12 .3 7LR 17 .1 7 17 .1 7 30 8. 24 30 0. 21 16 .9 9BTLA CD4 Fi l e: 06 051 Ga te: No Ga teQu a d % Ga ted % T otal X M ean X Ge o M ea n Y M eanUL 17 .9 2 84 .5 8UR 38 28 59 .6 4LL 82 .1 3 82 .1 3 LR 16 .8 5 16 .8 5 45 40 Fi l e: 06 051 Ga te: No Ga teQu a d % Ga ted % T otal X M ean X Ge o M ea n Y M eanUL 73 .3 2 73 .3 2 15 UR 11 .1 4 11 .1 4 47 42 89 .2 6LL 10 .7 9 10 .7 9 10 .6 7 17 .6 5LR 37 34 22 .8 8Fi l e: 06 051 Ga te: No Ga teQu a d % Ga ted % T otal X M ean X Ge o M ea n Y M eanUL 72 .5 4 72 .5 4 14 UR 12 .6 7 12 .6 7 47 43 90 .2 4LL 10 .0 2 10 .0 2 10 .7 8 18 .2 2LR 36 33 22 .4 9Fi l e: 06 051 Ga te: No Ga teQu a d % Ga ted % T otal X M ean X Ge o M ea n Y M eanUL 70 .2 6 70 .2 6 12 UR 10 .8 0 10 .8 0 45 41 82 .3 3LL 12 .9 9 12 .9 9 11 .2 5 18 .0 2LR 35 32 21 .8 30h 12h 24h The time of cells cultured with Con A 23 0 20 40 60 80 0 6 12 24 0 20 40 60 80 100 0 6 12 24 * ** ** activation time (h) activation time (h) % of BTLA+ in CD4+ T cells BLTA levels (MFI) C D Expression of BTLA during CD4+T cell activation Zeng Cun …Zhao Yong , J of Autoimmunity 2022 BTLA與 CD3ζ共同參與免疫突觸的形成 BTLA CD3ζ Overlay DAPI Resting T cell/APC/OVA Activated T cell/APC Activated T cell/APC/OVA Wu Tinghe … Zhao Yong Immunol and Cell Biol 2022 BTLA與 CD3ζ相互作用 IP AntiBTLA/Abctr WB : AntiCD3 ζ WB: AntiBTLA IP AntiCD3ζ /Abctr WB : AntiBTLA WB:AntiCD3 ζ Wu Tinghe … Zhao 。因此，在移植時，選擇 rap 作為藥物處理較合適。 開發(fā)同 /異種器官、組織及細(xì)胞臨床應(yīng)用潛能。 建立克服移植排斥及誘導(dǎo)移植免疫耐受的生物工程藥物及誘導(dǎo)方案。 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