Trager Jonathan D K, Zeevi Adriana, Jaffe Ronald, Rowe Marc I, Todo Satoru, Starzl Thomas E, Duquesnoy Rene J
Division of Clinical Immunopathology, Department of Pathology, and Department of Surgery, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania, U.S.A.
Clin Transplant. 1990;4:265-268.
We investigated the characteristics of lymphocytes propagated from biopsies of the mesenteric lymph nodes, liver, and ileum of a human multivisceral allograft in order to provide functional evidence for the presence or absence of rejection and graft-versus-host disease (GVHD). The recipient was a 39-month-old girl with secretory diarrhea due to microvillus inclusion disease and end-stage liver disease secondary to prolonged parenteral nutrition. She developed a multifocal posttransplant lymphoproliferative disorder (PTLD) and died 37 days after transplantation. Four pairs of sequential mesenteric lymph node and liver biopsies (13, 17, 24, and 33 d posttransplant) and a single ileal biopsy (31 d posttransplant) were placed in culture with recombinant interleukin-2 (rIL-2) and phytohemagglutinin (PHA). T-cell phenotyping of cultured cells showed that CD8+ cells became dominant in all three tissues. The alloreactivity of biopsy-grown cells was determined using the primed lymphocyte test (PLT) and cell-mediated lympholysis test (CML). The proliferative and/or cytolytic responses of biopsy-grown cells to donor but not recipient or third party cells provided evidence for rejection and absence of GVHD. This donor-specific alloreactivity was detected before there was histologic evidence of rejection and during the period of active lymphoproliferation. This study suggests that the functional characterization of graft-infiltrating lymphocytes is useful in defining the immunologic events following multivisceral transplantation.
我们研究了从人类多脏器同种异体移植的肠系膜淋巴结、肝脏和回肠活检组织中增殖的淋巴细胞的特征,以便为排斥反应和移植物抗宿主病(GVHD)的存在与否提供功能证据。受者是一名39个月大的女孩,因微绒毛包涵体病导致分泌性腹泻,并因长期肠外营养继发终末期肝病。她发生了多灶性移植后淋巴细胞增生性疾病(PTLD),并在移植后37天死亡。将四对连续的肠系膜淋巴结和肝脏活检组织(移植后13、17、24和33天)以及一次回肠活检组织(移植后31天)与重组白细胞介素-2(rIL-2)和植物血凝素(PHA)一起培养。对培养细胞进行T细胞表型分析显示,CD8+细胞在所有三种组织中均占主导地位。使用致敏淋巴细胞试验(PLT)和细胞介导的淋巴细胞溶解试验(CML)测定活检组织生长细胞的同种异体反应性。活检组织生长细胞对供体细胞而非受体或第三方细胞的增殖和/或细胞溶解反应为排斥反应和无GVHD提供了证据。这种供体特异性同种异体反应性在出现排斥反应的组织学证据之前以及活跃的淋巴细胞增殖期间就已检测到。这项研究表明,移植浸润淋巴细胞的功能特征有助于确定多脏器移植后的免疫事件。