端粒
特发性肺纤维化
医学
肺移植
免疫学
CD8型
移植
颗粒酶A
白细胞介素-7受体
肺
肿瘤科
颗粒酶B
T细胞
内科学
免疫系统
生物
遗传学
白细胞介素2受体
基因
作者
Mark E. Snyder,Michaela R. Anderson,Luke Benvenuto,Rachel M. Sutton,Anna Bondonese,R. Koshy,Roger A. Burke,Sarah Clifford,Andrew Craig,Carlo J. Iasella,S. Hannan,Iulia Popescu,Yingze Zhang,Pablo G. Sánchez,Jonathan K. Alder,John F. McDyer
标识
DOI:10.1016/j.healun.2023.08.001
摘要
PurposeMost idiopathic pulmonary fibrosis (IPF) lung transplant recipients (IPF-LTRs) have short telomere length (ST). Inherited mutations in telomere-related genes are associated with the development of T cell immunodeficiency. Despite this, IPF-LTRs with telomere-related rare variants are not protected from acute cellular rejection (ACR). We set out to determine the impact of both age and telomere length on the circulating T cell compartment and ACR burden of IPF-LTRs.MethodsWe identified 106 IPF-LTRs who had telomere length testing using flowFISH (57 with short telomeres, 49 with long telomers) as well as a subset from both cohorts who had cryopreserved PBMC at least one timepoint, 6 months post-transplantation. Circulating T cells from before transplantation and at 6 and 12 months-post transplantation were analyzed using multiparameter flow cytometry to study phenotype and functional capacity and bulk T cell receptor sequencing was performed to study repertoire diversity. Linear regression was used to study the relationship of age and telomere length on early (within 1 year) and late (between 1 and 2 years) acute cellular rejection.ResultsIPF-LTRs with ST were found to have premature ‘aging’ of their circulating T cell compartment, with age-agnostic elevations in post-transplant terminal differentiation of CD8+ T cells, increased granzyme B positivity of both CD8+ and CD4+ T cells, upregulation of the exhaustion marker, CD57, and chemotactic protein CCR5, and enhanced T cell receptor clonal expansion. Additionally, we found a significant decline in early ACR burden with increasing age, but only in the ST cohort.ConclusionIPF-LTRs with ST have premature ‘aging’ of their circulating T cell compartment post transplantation, and a clear age-related decline in ACR burden.
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