Tissue-resident memory T cell maintenance during antigen persistence requires both cognate antigen and interleukin-15.
Roger TieuQiang ZengDaqiang ZhaoGang ZhangNeda FeiziPriyanka ManandharAmanda L WilliamsBenjamin PoppMichelle A Wood-TrageserAnthony J DemetrisJ Yun TsoAaron J JohnsonLawrence P KaneKhodor I Abou-DayaWarren D ShlomchikMartin H OberbarnscheidtFadi G LakkisPublished in: Science immunology (2023)
Our understanding of tissue-resident memory T (T RM ) cell biology has been largely developed from acute infection models in which antigen is cleared and sterilizing immunity is achieved. Less is known about T RM cells in the context of chronic antigen persistence and inflammation. We investigated factors that underlie T RM maintenance in a kidney transplantation model in which T RM cells drive rejection. In contrast to acute infection, we found that T RM cells declined markedly in the absence of cognate antigen, antigen presentation, or antigen sensing by the T cells. Depletion of graft-infiltrating dendritic cells or interruption of antigen presentation after T RM cells were established was sufficient to disrupt T RM maintenance and reduce allograft pathology. Likewise, removal of IL-15 transpresentation or of the IL-15 receptor on T cells during T RM maintenance led to a decline in T RM cells, and IL-15 receptor blockade prevented chronic rejection. Therefore, antigen and IL-15 presented by dendritic cells play nonredundant key roles in CD8 T RM cell maintenance in settings of antigen persistence and inflammation. These findings provide insights that could lead to improved treatment of chronic transplant rejection and autoimmunity.
Keyphrases
- induced apoptosis
- dendritic cells
- cell cycle arrest
- immune response
- oxidative stress
- stem cells
- liver failure
- magnetic resonance
- single cell
- cell death
- patient safety
- magnetic resonance imaging
- case report
- cell proliferation
- working memory
- quality improvement
- hepatitis b virus
- combination therapy
- emergency medicine
- computed tomography