摘要
Tissue-resident memory T cells(T_(RM))play a key role in defense against pathogen invading barrier sites and other non-lymphoid tissues.How T_(RM)cells are maintained in various tissues,and how they relate to antigen-experienced memory T cells in lymphoid organs are not fully understood.By barcode-based lineage tracing and single-cell transcriptome analysis,we found a distinct population of CD69^(+)CD103^(+)virusspecific CD8^(+)T cells in draining lymph nodes(dLNs)following intranasal influenza infection.Intriguingly,these dLN T_(RM)cells and lung T_(RM)cells shared similar function-neutral barcode contents and transcriptomic features,implicating local circulation between the lung and dLNs in the maintenance of resident memory.Ablation of CXCR3 from CD8^(+)T cells,which impairs lung T_(RM)generation,severely reduced the abundance of dLN T_(RM)cells,suggesting that dLN T_(RM)cells are connected to lung T_(RM)cells by retrograde migration.Our screen for chemokines and chemokine receptors implicated the CCR5-CCL5 axis in promoting lung-to-dLN migration.Temporary CCR5 blockade by intratracheal administration of Maraviroc,a CCR5 inhibitor,reduced the abundance of dLN T_(RM)cells without affecting lung T_(RM)cells.By intratracheal cell transfer,CCR5-deficient CD8^(+)T cells were found impaired in lung-to-dLN migration.Finally,dLN T_(RM)cells actively participated in the secondary response and could reconstitute lung T_(RM)cells following influenza infection.Our results support a model in which lung-to-dLN T_(RM)retrograde migration helps maintain the CD8^(+)memory resident in the respiratory tract and optimizes the local Tcell response to reinfection.
基金
supported in part by the National Natural Science Foundation of China(T2225005)
the National Health Commission(2023ZD0519900,2023ZD0520300)
Shanxi Medical University-Tsinghua Collaborative Innovation Center for Frontier Medicine。
