de Silva Tharushi Ayanthika, Apte Simon, Voisey Joanne, Spann Kirsten, Tan Maxine, Chambers Daniel, O'Sullivan Brendan
Centre for Genomics and Personalised Health, Faculty of Health, School of Biomedical Sciences, Queensland University of Technology (QUT), Brisbane, QLD 4001, Australia.
Queensland Lung Transplant Service, Ground Floor, Clinical Sciences Building, The Prince Charles Hospital, Brisbane, QLD 4001, Australia.
Int J Mol Sci. 2024 Feb 20;25(5):2476. doi: 10.3390/ijms25052476.
Lung transplant recipients frequently encounter immune-related complications, including chronic lung allograft dysfunction (CLAD). Monitoring immune cells within the lung microenvironment is pivotal for optimizing post-transplant outcomes. This study examined the proportion of T cell subsets in paired bronchoalveolar lavage (BAL) and peripheral PBMC comparing healthy ( = 4) and lung transplantation patients ( = 6, no CLAD and = 14 CLAD) using 14-color flow cytometry. CD4+ T cell proportions were reduced in CD3 cells in both PBMC and BAL, and positive correlations were discerned between T cell populations in peripheral PBMC and BAL, suggesting the prospect of employing less invasive PBMC sampling as a means of monitoring lung T cells. Furthermore, regulatory T cells (Tregs) were enriched in BAL when compared to peripheral PBMC for transplant recipients. A parallel positive correlation emerged between Treg proportions in BAL and peripheral PBMC, underscoring potential avenues for monitoring lung Tregs. Finally, the most promising biomarker was the Teff (CD8+Granzyme B+)-Treg ratio, which was higher in both the PBMC and BAL of transplant recipients compared to healthy individuals, and increased in the patients with CLAD compared to no CLAD and healthy patients. Conclusions: Distinct T cell profiles in BAL and peripheral PBMC underscore the significance of localized immune monitoring in lung transplantation. The Teff (CD8+granzyme B+)-Treg ratio, particularly within the context of CLAD, emerges as a promising blood and BAL biomarker reflective of inflammation and transplant-related complications. These findings emphasize the imperative need for personalized immune monitoring strategies that tailored to address the unique immunological milieu in post-transplant lungs.
肺移植受者经常会遇到免疫相关并发症,包括慢性肺移植功能障碍(CLAD)。监测肺微环境中的免疫细胞对于优化移植后结果至关重要。本研究使用14色流式细胞术,比较了健康受试者(n = 4)和肺移植患者(n = 6,无CLAD和n = 14,有CLAD)配对的支气管肺泡灌洗(BAL)和外周血单个核细胞(PBMC)中T细胞亚群的比例。PBMC和BAL中CD3⁺细胞内的CD4⁺T细胞比例均降低,且外周血PBMC和BAL中的T细胞群体之间存在正相关,这表明采用侵入性较小的PBMC采样作为监测肺T细胞的一种手段具有前景。此外,与外周血PBMC相比,移植受者的BAL中调节性T细胞(Tregs)有所富集。BAL和外周血PBMC中的Treg比例之间出现了平行正相关,凸显了监测肺Tregs的潜在途径。最后,最有前景的生物标志物是效应性T细胞(Teff,CD8⁺颗粒酶B⁺)与Treg的比例,与健康个体相比,移植受者的PBMC和BAL中的该比例均更高,且与无CLAD和健康患者相比,有CLAD的患者该比例升高。结论:BAL和外周血PBMC中不同的T细胞谱强调了肺移植中局部免疫监测的重要性。Teff(CD8⁺颗粒酶B⁺)与Treg的比例,特别是在CLAD的背景下,成为反映炎症和移植相关并发症的有前景的血液和BAL生物标志物。这些发现强调了迫切需要针对移植后肺部独特免疫环境量身定制的个性化免疫监测策略。