Reinsmoen N L, Bolman R M, Savik K, Butters K, Hertz M
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis.
Transplantation. 1992 Jan;53(1):181-9. doi: 10.1097/00007890-199201000-00036.
Previous studies have demonstrated that donor antigen-specific primed-lymphocyte-test (PLT) reactivity of bronchoalveolar lavage lymphocytes is strongly associated with acute pulmonary rejection and with obliterative bronchiolitis (OB); however, a systematic analysis of PLT reactivity as being class I-or II-directed has not been performed. To assess reactivity directed against individual class I or II antigens, we tested a total of 67 BAL-derived lymphocyte samples from 26 recipients for alloreactivity in the PLT, using a pool of allogeneic cells and selected homozygous typing cells (HTCs) representing the HLA class I and II antigens expressed by the recipient and donor cells. The results obtained by PLT were correlated with the clinical status of the recipient with regard to rejection, infection, and OB. In 9 of 10 cases where transbronchial biopsy results were consistent with rejection, donor antigen-specific allogeneic PLT reactivity was observed and, more specifically, could be determined to be directed toward donor class II antigen in 8 of these cases. For 3 of 4 recipients tested chronologically, positive donor antigen-specific PLT reactivity was observed at the time of and 2-3 1/2 months prior to the diagnosis of rejection by transbronchial biopsy. During periods of acute infection, donor antigen-specific PLT reactivity was not observed; instead, non-specific PLT reactivity of BAL-derived cells (i.e., reactivity that did not correlate with any defined HLA antigens) was observed as well as reactivity associated with the self-antigens expressed by the recipients' cells. The PLT reactivity of BAL-derived cells from a recipient diagnosed with OB correlated specifically with one of the disparate donor class I antigens (HLA-B44). In 23 cases, BAL cells were propagated in the presence of autologous cells and rIL-2, thereby allowing for sufficient numbers of cells to test with a panel of 29 HTCs and to analyze for cell surface phenotype. The cultured BAL cells from 4 recipients undergoing a rejection episode demonstrated a predominant CD4+ phenotype consistent with the class II-directed reactivity observed in PLT. However, these results did not demonstrate a phenotype distinctive from the 7 BAL results obtained from 4 quiescent recipients. In marked contrast, the cultured BAL cells obtained from 4 recipients diagnosed with OB demonstrated a predominant CD8+ phenotype, with 60-92% of the cultured cells being CD8+. These results are consistent with the class I-directed reactivity observed in PLT.(ABSTRACT TRUNCATED AT 400 WORDS)
既往研究表明，支气管肺泡灌洗淋巴细胞的供体抗原特异性致敏淋巴细胞试验（PLT）反应性与急性肺排斥反应及闭塞性细支气管炎（OB）密切相关；然而，尚未对PLT反应性是针对I类还是II类抗原进行系统分析。为评估针对单个I类或II类抗原的反应性，我们使用一组同种异体细胞和代表受者及供体细胞所表达的HLA I类和II类抗原的选定纯合分型细胞（HTC），对来自26名受者的总共67份BAL来源的淋巴细胞样本进行了PLT中的同种异体反应性检测。PLT获得的结果与受者在排斥反应、感染和OB方面的临床状况相关。在10例经支气管活检结果与排斥反应一致的病例中，有9例观察到供体抗原特异性同种异体PLT反应性，更具体地说，其中8例可确定为针对供体II类抗原。在按时间顺序检测的4名受者中，有3名在经支气管活检诊断为排斥反应时及诊断前2至3个半月观察到阳性供体抗原特异性PLT反应性。在急性感染期间，未观察到供体抗原特异性PLT反应性；相反，观察到BAL来源细胞的非特异性PLT反应性（即与任何明确的HLA抗原无关的反应性）以及与受者细胞所表达的自身抗原相关的反应性。一名诊断为OB的受者的BAL来源细胞的PLT反应性与一种不同的供体I类抗原（HLA - B44）特异性相关。在23例病例中，BAL细胞在自体细胞和rIL - 2存在下增殖，从而获得足够数量的细胞以用一组29个HTC进行检测并分析细胞表面表型。4名经历排斥发作的受者的培养BAL细胞表现出主要为CD4 +表型，与PLT中观察到的针对II类抗原的反应性一致。然而，这些结果并未显示出与从4名静止受者获得的7份BAL结果有明显不同的表型。与之形成鲜明对比的是，从4名诊断为OB的受者获得的培养BAL细胞表现出主要为CD8 +表型，培养细胞中有
