Reinsmoen N L, Bolman R M, Savik K, Butters K, Hertz M I
Department of Surgery, University of Minnesota, Minneapolis 55455.
Transplantation. 1993 May;55(5):1040-4. doi: 10.1097/00007890-199305000-00017.
The primed lymphocyte test (PLT) has been used to detect donor antigen-specific reactivity of bronchoalveolar lavage (BAL) lymphocytes associated with acute lung rejection and obliterative bronchiolitis (OB). To identify more precisely the immunopathogenetic events related to these processes, we have determined the PLT alloreactivity of 162 BAL specimens from 40 recipients as being directed against individual class I or class II antigens. We used selected homozygous typing cells representing the specific HLA class I and II antigens expressed by the recipient and donor cells. Our previous studies demonstrated a predominant CD8+ cell population mediating class I donor antigen-specific reactivity, correlating with OB in 3 out of 3 recipients tested, and a predominant CD4+ cell population mediating class II donor antigen-specific reactivity, correlating with acute rejection episodes in 13 out of 15 recipients tested. The obstructive airway disease OB, which is frequently fatal, is identified histologically by the presence of small airway inflammation and fibrosis of the lamina propria and lumen, and is characterized clinically by rapidly progressive airflow obstruction. However, a subgroup of patients with histologically proven OB demonstrates stabilization or only minimal progression of airflow limitation after augmentation of their immunosuppressive regimen, usually with high-dose methylprednisolone. To further characterize this subgroup, we tested the BAL-derived lymphocytes from 4 of these patients and observed PLT reactivity that correlated with the class II antigens of the donor, in contrast to the predominant donor class I antigen-specific PLT reactivity of patients with progressive OB. The distinct patterns of PLT reactivity observed for the BAL-derived lymphocytes from patients with the progressive versus the less progressive form of OB suggest that more than one immune process or perhaps different cell targets are involved. Alternatively, these clinical and in vitro findings may represent different stages of the same disease process. Taken together, these results suggest that distinct immunopathogenetic events may be occurring during acute lung rejection and OB.
致敏淋巴细胞试验（PLT）已被用于检测与急性肺排斥反应和闭塞性细支气管炎（OB）相关的支气管肺泡灌洗（BAL）淋巴细胞的供体抗原特异性反应性。为了更精确地识别与这些过程相关的免疫发病机制事件，我们测定了来自40名受者的162份BAL标本的PLT同种异体反应性，发现其针对个体I类或II类抗原。我们使用了选定的纯合分型细胞，这些细胞代表受者和供体细胞表达的特定HLA I类和II类抗原。我们之前的研究表明，主要是CD8 +细胞群体介导I类供体抗原特异性反应性，在3名受试受者中有3名与OB相关；主要是CD4 +细胞群体介导II类供体抗原特异性反应性，在15名受试受者中有13名与急性排斥反应发作相关。阻塞性气道疾病OB通常是致命的，在组织学上通过小气道炎症以及固有层和管腔的纤维化来识别，在临床上的特征是气流阻塞迅速进展。然而，一组经组织学证实为OB的患者在增加免疫抑制方案（通常是高剂量甲基强的松龙）后，气流受限表现出稳定或仅轻微进展。为了进一步表征这一亚组患者，我们检测了其中4名患者的BAL来源淋巴细胞，观察到PLT反应性与供体的II类抗原相关，这与进行性OB患者主要的供体I类抗原特异性PLT反应性形成对比。进行性OB患者与进展较慢形式OB患者的BAL来源淋巴细胞观察到的不同PLT反应性模式表明，涉及不止一种免疫过程或可能不同的细胞靶点。或者，这些临床和体外研究结果可能代表同一疾病过程的不同阶段。综上所述，这些结果表明在急性肺排斥反应和OB期间可能发生不同的免疫发病机制事件。
