Rationale: Tissue-resident memory T cells (T RM ) play a critical role in the defense against inhaled pathogens. The isolation and study of human lung tissue-resident memory T cells and lung-resident macrophages (M LR ) are limited by experimental constraints.Objectives: To characterize the spatial and functional relationship between M LR and human lung tissue-resident memory T cells using ex vivo lung perfusion (EVLP).Methods: T RM and M LR were isolated using EVLP and intraperfusate-labeled CD45 antibody. Cells isolated after 6 hours of EVLP were analyzed using spectral flow cytometry. Spatial relationships between CD3 1 and CD68 1 cells were explored with multiplexed immunohistochemistry. Functional relationships were determined by using coculture and T-cell-receptor complex signal transduction.Measurements and Main Results: Lungs from 8 researchconsenting organ donors underwent EVLP for 6 hours. We show that human lung T RM and M LR colocalize within the human lung, preferentially around the airways. Furthermore, we found that human lung CD8 1 T RM are composed of two functionally distinct populations on the basis of PD1 (programed cell death receptor 1) and ZNF683 (HOBIT) protein expression. We show that M LR provide costimulatory signaling to PD1 hi CD4 1 and CD8 1 lung T RM, , augmenting the effector cytokine production and degranulation of T RM .Conclusions: EVLP provides an innovative technique to study resident immune populations in humans. Human M LR colocalize with and provide costimulation signaling to T RM , augmenting their effector function.
Background
Despite advances in critical care for acute respiratory distress syndrome (ARDS), some survivors in the acute phase are unable to wean from extracorporeal membrane oxygenation (ECMO) or mechanical ventilation. To date, little is known regarding whether lung transplantation confers a survival benefit for irreversible ARDS.
Methods
This retrospective study was conducted using the United Network for Organ Sharing database (May 2005–December 2018). Patients with restrictive lung disease were divided into two groups: patients with and without ARDS. Propensity score matching identified recipients without ARDS for the control group.
Results
A total of 63 patients with ARDS were waitlisted for lung transplantation, while 39 received a lung transplant after a median waitlist duration of 8 days. Seventy‐eight patients were matched as controls. In the ARDS group, the median age was 30 years, and the median lung allocation score was 88.4. Among the 39 recipients, 30 (76.9%) received ECMO support prior to transplantation. Lung transplantation for ARDS and restrictive lung disease showed similar 90‐day (87.2% vs. 88.5%, p = .80), 1‐year (82.1% vs. 85.9%, p = .52), and 3‐year (69.2% vs. 65.4%, p = .94) survival rates.
Conclusions
Lung transplantation provides acceptable outcomes in selected patients with irreversible ARDS.
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