T and B lymphocyte dynamics after genetically-modified pig-to-baboon kidney xenotransplantation with an anti-CD40mAb-based immunosuppressive regimen.
T and B lymphocyte dynamics after genetically-modified pig-to-baboon kidney xenotransplantation with an anti-CD40mAb-based immunosuppressive regimen.
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DOI：
10.1016/j.trim.2022.101545
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发表时间：
2022-04
影响因子：
1.5
通讯作者：
Hara, Hidetaka
中科院分区：
文献类型：
--
作者：
Jagdale, Abhijit;Huy Nguyen;Iwase, Hayato;Foote, Jeremy B.;Yamamoto, Takayuki;Javed, Mariyam;Ayares, David;Anderson, Douglas J.;Eckhoff, Devin E.;Cooper, David K. C.;Hara, Hidetaka
目的是监测狒狒中T/B淋巴细胞在抗胸腺细胞球蛋白（ATG）和抗CD 20 mAb（利妥昔单抗）耗竭后的恢复情况，然后进行猪肾移植和基于抗CD 40 mAb的方案维持治疗。在狒狒（n=14）中，使用ATG和抗CD 20 mAb进行诱导，并使用（i）抗CD 40 mAb、（ii）雷帕霉素和（iii）甲泼尼龙进行维持。术后随访6个月，或直至发生排斥反应或其他并发症。每隔一段时间收集狒狒血液，通过流式细胞术测量T/B细胞和亚群。在接受相同免疫抑制方案的狒狒（n=10）中进行的一项单独研究中，检查了PBMC、淋巴结和脾脏中的T/B淋巴细胞群。诱导治疗后，总淋巴细胞计数和CD 3+、CD 4+和CD 8 +T细胞绝对数下降> 80%，无CD 22 +B细胞残留（均p<0.001）。T细胞数量在早期开始恢复，但在2个月内血液中没有CD 22 +B细胞。即使发生排斥反应，T和B细胞的恢复仍保持在基线的<30%（p<0.001）。在6个月时，效应记忆CD 8 +T细胞比其他T细胞亚群增加更多，但更大比例的B细胞是幼稚的。与血液和脾脏相反，淋巴结中的T和B细胞未耗尽。ATG和抗CD 20 mAb有效地降低了血液中的T和B淋巴细胞，并且在存在抗CD 40 mAb维持治疗的情况下，抑制了这些细胞的恢复。效应记忆CD 8 +T细胞的恢复可能对移植物的长期存活不利。
The aim was to monitor recovery of T/B lymphocytes in baboons after depletion by anti-thymocyte globulin (ATG) and anti-CD20mAb (Rituximab), followed by pig kidney transplantation and maintenance therapy with an anti-CD40mAb-based regimen. In baboons (n=14), induction was with ATG and anti-CD20mAb, and maintenance with (i) anti-CD40mAb, (ii) rapamycin, and (iii) methylprednisolone. Follow-up was for 6 months, or until rejection or other complication developed. Baboon blood was collected at intervals to measure T/B cells and subsets by flow cytometry. In a separate study in baboons receiving the same immunosuppressive regimen (n=10), the populations of T/B lymphocytes in PBMCs, lymph nodes, and spleen were examined. After induction therapy, the total lymphocyte count and the absolute numbers of CD3+, CD4+, and CD8+T cells fell by >80%, and no CD22+B cells remained (all p<0.001). T cell numbers began to recover early, but no CD22+B cells were present in the blood for 2 months. Recovery of both T and B cells remained at <30% of baseline (p<0.001), even if rejection developed. At 6 months, effector memory CD8+T cells had increased more than other T cell subsets, but a greater percentage of B cells were naïve. In contrast to blood and spleen, T and B cells were not depleted in lymph nodes. ATG and anti-CD20mAb effectively decreased T and B lymphocytes in the blood and, in the presence of anti-CD40mAb maintenance therapy, recovery of these cells was inhibited. The recovery of effector memory CD8+T cells may be detrimental to long-term graft survival.
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DOI：
10.1111/j.1600-6143.2011.03846.x
发表时间：
2012-03
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Mohiuddin MM;Corcoran PC;Singh AK;Azimzadeh A;Hoyt RF Jr;Thomas ML;Eckhaus MA;Seavey C;Ayares D;Pierson RN 3rd;Horvath KA
通讯作者：
Horvath KA
影响因子：
8.8
作者：
Ayasoufi, K.;Yu, H.;Valujskikh, A.
通讯作者：
Valujskikh, A.
影响因子：
3.9
作者：
Ezzelarab, Mohamed B.;Ekser, Burcin;Cooper, David K. C.
通讯作者：
Cooper, David K. C.
共刺激阻碍改变了生发中心的反应，并防止抗体介导的排斥反应。
DOI：
10.1111/ajt.12526
发表时间：
2014-01
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Kim EJ;Kwun J;Gibby AC;Hong JJ;Farris AB 3rd;Iwakoshi NN;Villinger F;Kirk AD;Knechtle SJ
通讯作者：
Knechtle SJ
影响因子：
82.9
作者：
Liu, Chengyang;Noorchashm, Hooman;Naji, Ali
通讯作者：
Naji, Ali