Department of Medicine, University of Pittsburgh, Pittsburgh, PA.
Department of Immunology, University of Pittsburgh, Pittsburgh, PA.
J Exp Med. 2022 Apr 4;219(4). doi: 10.1084/jem.20212059. Epub 2022 Mar 14.
Acute cellular rejection is common after lung transplantation and is associated with an increased risk of early chronic rejection. We present combined single-cell RNA and TCR sequencing on recipient-derived T cells obtained from the bronchoalveolar lavage of three lung transplant recipients with rejection and compare them with T cells obtained from the same patients after treatment of rejection with high-dose systemic glucocorticoids. At the time of rejection, we found an oligoclonal expansion of cytotoxic CD8+ T cells that all persisted as tissue resident memory T cells after successful treatment. Persisting CD8+ allograft-resident T cells have reduced gene expression for cytotoxic mediators after therapy with glucocorticoids but accumulate around airways. This clonal expansion is discordant with circulating T cell clonal expansion at the time of rejection, suggesting in situ expansion. We thus highlight the accumulation of cytotoxic, recipient-derived tissue resident memory T cells within the lung allograft that persist despite the administration of high-dose systemic glucocorticoids. The long-term clinical consequences of this persistence have yet to be characterized.
急性细胞排斥反应在肺移植后很常见，并且与早期慢性排斥反应的风险增加有关。我们对 3 名肺移植受者支气管肺泡灌洗液中接受者来源的 T 细胞进行了单细胞 RNA 和 TCR 测序，并将其与用大剂量全身糖皮质激素治疗排斥反应后从同一患者获得的 T 细胞进行了比较。在排斥反应时，我们发现细胞毒性 CD8+T 细胞的寡克隆扩增，在成功治疗后所有这些细胞都持续存在为组织驻留记忆 T 细胞。在用糖皮质激素治疗后，持续存在的 CD8+同种异体驻留 T 细胞的细胞毒性介质的基因表达减少，但在气道周围聚集。这种克隆扩增与排斥反应时循环 T 细胞克隆扩增不一致，提示原位扩增。因此，我们强调了在肺移植中积累的细胞毒性、受者来源的组织驻留记忆 T 细胞，尽管给予大剂量全身糖皮质激素，但仍持续存在。这种持续性的长期临床后果尚未确定。
