Trzonkowski P, Zilvetti M, Chapman S, Wieckiewicz J, Sutherland A, Friend P, Wood K J
Transplantation Research Immunology Group and Oxford Transplant Centre, Nuffield Department of Surgery, University of Oxford, UK.
Am J Transplant. 2008 Feb;8(2):338-47. doi: 10.1111/j.1600-6143.2007.02078.x.
Alemtuzumab (CAMPATH-1H) is a depleting agent introduced recently in transplantation and often used with reduced maintenance immunosuppression. In the current study we investigated the immune response of 13 kidney allograft recipients treated with alemtuzumab followed by weaned immunosuppression with reduced dose of mycophenolate mofetil (MMF) and tacrolimus. Tacrolimus was switched to sirolimus at 6 months and MMF withdrawn at 12 months after transplantation. We found that after alemtuzumab induction the recovery of CD8(+) T cells was much faster than that of CD4(+) T cells. It was complete 6 months posttransplant while CD4(+) T cells did not fully recover even 15 months posttransplant. Repopulating CD8(+) T cells were mainly of immunosenescent CD28(-)CD8(+) phenotype. In a series of in vitro experiments we showed that CD28(-)CD8(+) T cells might suppress proliferation of CD4(+) T cells. There were three successfully treated acute rejections during the study (first at +70 day, two others +12 months) that occurred in patients with the lowest level of CD28(-)CD8(+) T cells. We hypothesize that expanded CD28(-)CD8(+) T cells might compete for 'immune space' with CD4(+) T cells suppressing their proliferation and therefore delaying CD4(+) T-cells recovery. This delay might be associated with the clinical outcome as CD4(+) T cells, notably CD4(+) T effector memory cells, were shown to be associated with rejection.
阿仑单抗（CAMPATH-1H）是一种最近引入移植领域的清除剂，常用于减少维持性免疫抑制。在本研究中，我们调查了13例接受阿仑单抗治疗，随后逐渐减少霉酚酸酯（MMF）和他克莫司剂量进行免疫抑制的肾移植受者的免疫反应。移植后6个月将他克莫司换为西罗莫司，12个月后停用MMF。我们发现，阿仑单抗诱导后，CD8(+) T细胞的恢复比CD4(+) T细胞快得多。移植后6个月恢复完成，而CD4(+) T细胞甚至在移植后15个月仍未完全恢复。重新填充的CD8(+) T细胞主要是免疫衰老的CD28(-)CD8(+)表型。在一系列体外实验中，我们表明CD28(-)CD8(+) T细胞可能抑制CD4(+) T细胞的增殖。研究期间有3例急性排斥反应得到成功治疗（第一例在+70天，另外两例在+12个月），发生在CD28(-)CD8(+) T细胞水平最低的患者中。我们推测，扩增的CD28(-)CD8(+) T细胞可能与CD4(+) T细胞竞争“免疫空间”，抑制其增殖，从而延迟CD4(+) T细胞的恢复。这种延迟可能与临床结果相关，因为CD4(+) T细胞，尤其是CD4(+) T效应记忆细胞，已被证明与排斥反应有关。
