Alba A, Morales J, Fierro A, Zehnder C, Cao C, Orozco R, Herzog C, Calabrán L, Contreras L, Buckel E
Centro de Trasplante, Clínica Las Condes, Santiago, Chile.
Transplant Proc. 2010 Jan-Feb;42(1):253-6. doi: 10.1016/j.transproceed.2009.12.046.
Organ transplantation success depends principally on avoiding rejection, a purpose almost accomplished with immunosuppressant therapy. Nevertheless, drug side effects have promoted the search for other mechanisms to restrain alloresponses. T-regulatory cells (Treg) might exert that function. Campath 1H (C1H) induces Treg proliferation in the period subsequent to T-cell depletion following C1H administration. In the present study, the status of Treg and de novo HLA antibody production was determined posttransplantation when T-cell repopulation had been completed. In 14 patients, the following parameters were analyzed: renal function, rejection, Treg, panel-reactive antibody (PRA), and HLA antibodies. Patient and graft survivals were 100%. At the moment of Treg determination (20 months following transplant) the mean tacrolimus level was 8.4 ng/mL. One patient experienced an antibody-mediated rejection at 15 months after transplantation while having 3.2% Treg, with excellent treatment responses. Mean leukocyte and lymphocyte counts were 5752 and 1183 cells/mm(3); the mean peripheral blood percentage of Treg of 7.1% +/- 5.9% was not different from that observed in subjects without induction (mean 5.5% +/- 2.5%). Three patients (21%) showed Treg greater than 8.0%. In seven patients, we compared Treg at 4 and 20 months posttransplant, observing a decline from a mean of 19.9% to 5.9% (P = .05). In seven recipients, posttransplant PRA was determined; five of them became "de novo" sensitized, three with a mean class I PRA of 16% and two with a mean class II PRA of 37%. In conclusion, patient and graft survivals were excellent, mean Treg percentage was not elevated with results lower than in the early posttransplant period. Rejection incidence was negligible. Late "de novo" sensitization occurred in 70% showing that B cell-mediated alloresponses were only partially controlled among recipients induced with C1H even when associated with sustained anticalcineurin treatment.
器官移植的成功主要取决于避免排斥反应，免疫抑制疗法几乎实现了这一目标。然而，药物副作用促使人们寻找其他抑制同种异体反应的机制。调节性T细胞（Treg）可能发挥这种功能。Campath 1H（C1H）在给予C1H后T细胞耗竭后的时期诱导Treg增殖。在本研究中，在T细胞重新填充完成后，确定移植后Treg的状态和新生HLA抗体的产生。对14例患者分析了以下参数：肾功能、排斥反应、Treg、群体反应性抗体（PRA）和HLA抗体。患者和移植物存活率均为100%。在测定Treg时（移植后20个月），他克莫司的平均水平为8.4 ng/mL。一名患者在移植后15个月发生抗体介导的排斥反应，此时Treg为3.2%，治疗反应良好。白细胞和淋巴细胞平均计数分别为5752和1183个细胞/mm³；Treg在外周血中的平均百分比为7.1%±5.9%，与未进行诱导的受试者中观察到的百分比（平均5.5%±2.5%）无差异。3例患者（21%）的Treg大于8.0%。在7例患者中，我们比较了移植后4个月和20个月时的Treg，观察到其从平均19.9%下降至5.9%（P = 0.05）。在7例受者中测定了移植后的PRA；其中5例发生“新生”致敏，3例I类PRA平均为16%，2例II类PRA平均为37%。总之，患者和移植物存活率良好，Treg平均百分比未升高，结果低于移植后早期。排斥反应发生率可忽略不计。70%的患者发生晚期“新生”致敏，这表明即使联合持续的钙调神经磷酸酶抑制剂治疗，在接受C1H诱导的受者中，B细胞介导的同种异体反应仅得到部分控制。
