Modulation of tissue resident memory T cells by glucocorticoids after acute cellular rejection in lung transplantation

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 rej...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of experimental medicine 2022-04, Vol.219 (4)
Main Authors: Snyder, Mark E, Moghbeli, Kaveh, Bondonese, Anna, Craig, Andrew, Popescu, Iulia, Fan, Li, Tabib, Tracy, Lafyatis, Robert, Chen, Kong, Trejo Bittar, Humberto E, Lendermon, Elizabeth, Pilewski, Joseph, Johnson, Bruce, Kilaru, Silpa, Zhang, Yingze, Sanchez, Pablo G, Alder, Jonathan K, Sims, Peter A, McDyer, John F
Format: Article
Language:English
Subjects:
CD8-Positive T-Lymphocytes - metabolism
Glucocorticoids - metabolism
Graft Rejection - genetics
Graft Rejection - metabolism
Humans
Lung Transplantation
Memory T Cells
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.20212059