Hasegawa S, Ockner D M, Ritter J H, Patterson G A, Trulock E P, Cooper J D, Wick M R
Division of Cardiothoracic Surgery, Washington University Medical Center, St Louis, Mo, USA.
Arch Pathol Lab Med. 1995 May;119(5):432-9.
Currently, the bronchiolitis obliterans syndrome (BOS) of chronic airway rejection represents the most significant obstacle to the long-term function of isolated pulmonary allografts in humans. Between 20% and 30% of recipients are affected by this condition. To define the possible pathogenetic role of altered expression of class II major histocompatibility complex antigens (ie, HLA-DR) in BOS, the authors studied well-characterized examples of this process immunohistologically.
Eleven BOS specimens were compared with seven controls, represented by allografts with no pathologic abnormalities taken from patients with normal posttransplant respiratory function, as well as 14 biopsies showing acute rejection. In addition, immunophenotypic subtyping of lymphocytes in all specimens was undertaken.
Control tissues exhibited variable but weak expression of HLA-DR in bronchiolar epithelium and alveolar pneumocytes. In comparison, immunostaining for class II major histocompatibility complex antigens in BOS showed no statistically significant differences, whereas the 14 examples of acute rejection manifested intense HLA-DR expression in epithelia and endothelial cells. The numbers of intrabronchiolar and peribronchiolar lymphocytes were clearly higher in both acute rejection and BOS than in controls, but these cells differed in lineage in the two rejection states. Acute rejection showed an obvious preponderance of CD43-positive T lymphocytes, whereas lymphoid cells in BOS were a relatively equal mixture of CD20-positive B cells and CD43-positive T cells. Moreover, incipient peribronchiolar B-cell follicles were observed in BOS. Natural killer (CD57-positive) lymphocytes were rare in all specimens.
These data suggest that alterations in HLA-DR expression probably do not play a central role in the genesis of BOS, as they do in acute rejection. In contrast, the results of lymphocyte immunophenotyping and correlative histologic findings in BOS suggest that both T cells and B lymphocytes may be involved in the mechanism of chronic airway rejection.
目前，慢性气道排斥反应所致的闭塞性细支气管炎综合征（BOS）是阻碍人类孤立肺移植长期功能的最主要障碍。20%至30%的受者受此病症影响。为明确II类主要组织相容性复合体抗原（即HLA-DR）表达改变在BOS中可能的致病作用，作者采用免疫组织学方法对该过程的典型病例进行了研究。
将11例BOS标本与7个对照进行比较，对照包括取自移植后呼吸功能正常患者且无病理异常的同种异体移植物，以及14例显示急性排斥反应的活检标本。此外，对所有标本中的淋巴细胞进行免疫表型分型。
对照组织在细支气管上皮和肺泡上皮细胞中HLA-DR表达各异但较弱。相比之下，BOS中II类主要组织相容性复合体抗原的免疫染色无统计学显著差异，而14例急性排斥反应在上皮细胞和内皮细胞中表现为强烈的HLA-DR表达。急性排斥反应和BOS中细支气管内及细支气管周围淋巴细胞数量均明显高于对照，但这两种排斥状态下的这些细胞谱系不同。急性排斥反应中CD43阳性T淋巴细胞明显占优势，而BOS中的淋巴细胞是CD20阳性B细胞和CD43阳性T细胞相对均等的混合。此外，在BOS中观察到初期的细支气管周围B细胞滤泡。自然杀伤（CD57阳性）淋巴细胞在所有标本中均少见。
这些数据表明，HLA-DR表达改变可能不像在急性排斥反应中那样在BOS的发生中起核心作用。相反，BOS中淋巴细胞免疫表型分型结果及相关组织学发现提示，T细胞和B淋巴细胞可能均参与慢性气道排斥反应机制。
