Abstract:
RATIONALE:Tissue resident memory T cells 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 is limited by experimental constraints. OBJECTIVES:To characterize the spatial and functional relationship between lung resident macrophages and human lung tissue resident memory T cells using ex-vivo lung perfusion. METHODS:Tissue resident memory T cells and lung resident macrophages were isolated using ex-vivo lung perfusion and intra-perfusate labeled CD45 antibody. Cells isolated after 6 hours of ex-vivo lung perfusion were analyzed using spectral flow cytometry. Spatial relationships between CD3+ and CD68+ cells were explored with multiplexed immunohistochemistry (IHC). Functional relationships were determined by co-culture and T cell receptor complex signal transduction. MEASUREMENTS AND MAIN RESULTS:Lungs from 8 research-consented organ donors underwent ex-vivo lung perfusion for 6 hours. We show that human lung TRM and MLR co-localize within the human lung, preferentially around the airways. Furthermore, we found that human lung CD8+ TRM are composed of two functionally distinct populations based on PD1 and ZNF683 (HOBIT) protein expression. We show that MLR provide co-stimulatory signaling to PD1hi CD4+ and CD8+ lung TRM, augmenting TRM effector cytokine production and degranulation. CONCLUSIONS:Ex-vivo lung perfusion provides an innovative technique to study resident immune populations in humans. Human lung resident macrophages co-localize with and provide co-stimulation signaling to tissue resident memory T cells, augmenting their effector function.
journal_name
Am J Respir Crit Care Medauthors
Snyder ME,Sembrat J,Noda K,Myerburg MM,Craig A,Mitash N,Harano T,Furukawa M,Pilewski J,McDyer J,Rojas M,Sanchez Pdoi
10.1164/rccm.202006-2403OCsubject
Has Abstractpub_date
2020-12-11 00:00:00eissn
1073-449Xissn
1535-4970pub_type
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