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

ME Snyder, K Moghbeli, A Bondonese… - Journal of Experimental …, 2022 - rupress.org
ME Snyder, K Moghbeli, A Bondonese, A Craig, I Popescu, L Fan, T Tabib, R Lafyatis…
Journal of Experimental Medicine, 2022rupress.org
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 …
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.
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