Dal Col R H, Zeevi A, Rabinowich H, Herlan D B, Yousem S A, Griffith B P
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania.
Ann Thorac Surg. 1990 May;49(5):754-8. doi: 10.1016/0003-4975(90)90015-x.
Ten beagle dogs underwent left unilateral lung transplantation and were treated with cyclosporine and azathioprine. After three days, cyclosporine administration was discontinued and azathioprine administration was maintained at a suboptimal dose to allow a graded response to the pulmonary allograft. Dogs were monitored by chest roentgenogram, bronchoalveolar lavage (BAL), and sampling of peripheral blood lymphocytes at weekly intervals. Open lung biopsies also were performed at weekly intervals in 5 of the dogs. Lymphocytes from the BAL and peripheral blood and those grown in culture from open and transbronchial biopsy specimens were tested for donor-specific cytotoxicity (DSC) by testing their responsiveness to lymphocytes from their donor. Rejection was confirmed in all animals. Donor-specific cytotoxicity became detectable in all animals in either the BAL fluid or biopsy specimens. An abnormal chest roentgenogram developed in 9 dogs, but not until after DSC was detected in the BAL in 7. In the open biopsy specimens tested for DSC, all exhibited DSC synchronous with the first changes noted on chest roentgenogram. Donor-specific cytotoxicity was sensitive for detecting rejection in 8 of 9 dogs in the BAL and in 5 of 5 dogs in the open biopsy specimens. Based on these results, 3 additional dogs were maintained on cyclosporine. Two of these dogs did not reject their transplants and had no evidence of DSC. We conclude that donor-specific functional assays provide an advance over less sensitive clinical techniques.
十只比格犬接受了左肺单侧移植，并接受环孢素和硫唑嘌呤治疗。三天后，停止使用环孢素，硫唑嘌呤以次优剂量维持给药，以观察对肺移植的分级反应。每周通过胸部X线片、支气管肺泡灌洗（BAL）和外周血淋巴细胞采样对犬进行监测。五只犬还每周进行一次开放性肺活检。通过检测BAL和外周血中的淋巴细胞以及从开放性和经支气管活检标本培养的淋巴细胞对供体淋巴细胞的反应性，来检测供体特异性细胞毒性（DSC）。所有动物均证实发生了排斥反应。在所有动物的BAL液或活检标本中均检测到了供体特异性细胞毒性。9只犬出现了异常的胸部X线片，但直到7只犬的BAL中检测到DSC后才出现。在检测DSC的开放性活检标本中，所有标本均显示DSC与胸部X线片上首次发现的变化同步。在BAL中，供体特异性细胞毒性对9只犬中的8只检测排斥反应敏感，在开放性活检标本中对5只犬中的5只敏感。基于这些结果，另外3只犬继续使用环孢素。其中两只犬未发生移植排斥反应，也没有DSC的证据。我们得出结论，供体特异性功能测定比敏感性较低的临床技术更具优势。
