期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 219, 期 4, 页码 -出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20212059
关键词
-
资金
- National Intitutes of Health [K23 HL151750-01, 1R01HL133184]
During acute cellular rejection after lung transplantation, there is an intra-allograft oligoclonal expansion of cytotoxic CD8(+) T cells. Despite treatment with systemic glucocorticoids, expanded T cell clones persist as transcriptionally reprogrammed, airway-centric tissue resident memory T cells.
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. During acute cellular rejection after lung transplantation, there is an intra-allograft oligoclonal expansion of cytotoxic CD8(+) T cells. Despite treatment with systemic glucocorticoids, expanded T cell clones persist as transcriptionally reprogrammed, airway-centric tissue resident memory T cells.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据