Rate of recipient-derived alveolar macrophage development and major histocompatibility complex cross-decoration after lung transplantation in humans.
Rate of recipient-derived alveolar macrophage development and major histocompatibility complex cross-decoration after lung transplantation in humans.
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DOI：
10.1111/ajt.16812
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发表时间：
2022-03
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肺泡巨噬细胞(AM)在肺组织动态平衡、宿主防御和调节肺损伤中发挥重要作用。移植后AM周转率(循环单核细胞替代供者AM)尚不完全清楚。此外，受体来源的肺巨噬细胞再增殖的解剖学模式还没有报道，它们积累和呈现供体主要组织相容性复合体的能力(我们称之为MHC交叉修饰)也没有报道。我们纵向研究了肺移植受者的支气管肺泡灌洗(BAL)和活检标本中的髓样含量，发现同种异体肺移植的AM周转率为双相率，且在围手术期迅速周转，既有诱导性免疫抑制的类型，又有移植物功能障碍的存在。我们发现，具有细胞表面AM表型的受者髓系细胞以一种无序的模式重新填充肺，主要由大的细胞团组成。最后，我们发现受体AM摄取并呈递供体多肽-MHC复合体，但不能独立地通过循环受体T细胞诱导体外同种异体反应。
Alveolar macrophages (AM) play critical roles in lung tissue homeostasis, host defense, and modulating lung injury. The rate of AM turnover (donor AM replacement by circulating monocytes) after transplantation has been incompletely characterized. Furthermore, the anatomic pattern of recipient-derived lung macrophages repopulation has not been reported, nor has their ability to accumulate and present donor major histocompatibility complex (a process we refer to as MHC cross-decoration). We longitudinally characterized the myeloid content of bronchoalveolar lavage (BAL) and biopsy specimens of lung transplant recipients and found a biphasic rate in AM turnover in the allograft, with a rapid turnover perioperatively, accelerated by both the type of induction immunosuppression and the presence of primary graft dysfunction. We found that recipient myeloid cells with cell surface AM phenotype repopulated the lung in a disorganized pattern, comprised mainly of large clusters of cells. Finally, we show that recipient AM take up and present donor peptide-MHC complexes yet are not able to independently induce an in vitro alloreactive response by circulating recipient T cells.
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