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

Autor:	Snyder ME; Department of Medicine, University of Pittsburgh, Pittsburgh, PA.; Department of Immunology, University of Pittsburgh, Pittsburgh, PA.; Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA., Moghbeli K; Department of Medicine, University of Pittsburgh, Pittsburgh, PA., Bondonese A; Department of Medicine, University of Pittsburgh, Pittsburgh, PA., Craig A; Department of Medicine, University of Pittsburgh, Pittsburgh, PA., Popescu I; Department of Medicine, University of Pittsburgh, Pittsburgh, PA., Fan L; Department of Medicine, University of Pittsburgh, Pittsburgh, PA., Tabib T; Department of Medicine, University of Pittsburgh, Pittsburgh, PA., Lafyatis R; Department of Medicine, University of Pittsburgh, Pittsburgh, PA., Chen K; Department of Medicine, University of Pittsburgh, Pittsburgh, PA., Trejo Bittar HE; Department of Pathology, University of Pittsburgh, Pittsburgh, PA., Lendermon E; Department of Medicine, University of Pittsburgh, Pittsburgh, PA., Pilewski J; Department of Medicine, University of Pittsburgh, Pittsburgh, PA., Johnson B; Department of Medicine, University of Pittsburgh, Pittsburgh, PA., Kilaru S; Department of Medicine, University of Pittsburgh, Pittsburgh, PA., Zhang Y; Department of Medicine, University of Pittsburgh, Pittsburgh, PA., Sanchez PG; Department of Surgery, University of Pittsburgh, Pittsburgh, PA., Alder JK; Department of Medicine, University of Pittsburgh, Pittsburgh, PA., Sims PA; Department of Systems Biology, Columbia University Irving Medical Center, New York, NY., McDyer JF; Department of Medicine, University of Pittsburgh, Pittsburgh, PA.; Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2022 Apr 04; Vol. 219 (4). Date of Electronic Publication: 2022 Mar 14.
DOI:	10.1084/jem.20212059
Abstrakt:	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. Competing Interests: Disclosures: R. Lafyatis reported grants from Moderna, Corbus, Formation, Regeneron, Astra Zeneca, Pfizer, Kiniksa, and Mitsubushi; and personal fees from Pfizer, Boehringer-Ingelheim, Sanofi, Boehringer-Mannheim, Merck, Biogen, Genentech, and Bristol Myers Squibb outside the submitted work. J. Pilewski reported grants from Breath Therapeutics and Incyte outside the submitted work. J.K. Alder reported grants from National Heart, Lung, and Blood Institute during the conduct of the study. No other disclosures were reported. (© 2022 Snyder et al.)
Databáze:	MEDLINE
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