Tissue-resident memory T cell maintenance during antigen persistence requires both cognate antigen and interleukin-15

SCIENCE IMMUNOLOGY(2023)

Cited 4|Views31
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Abstract
Our understanding of tissue-resident memory T (TRM) cell biology has been largely developed from acute infec-tion models in which antigen is cleared and sterilizing immunity is achieved. Less is known about TRM cells in the context of chronic antigen persistence and inflammation. We investigated factors that underlie TRM mainte-nance in a kidney transplantation model in which TRM cells drive rejection. In contrast to acute infection, we found that TRM 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 TRM cells were established was sufficient to disrupt TRM maintenance and reduce allograft pathology. Like-wise, removal of IL-15 transpresentation or of the IL-15 receptor on T cells during TRM maintenance led to a decline in TRM cells, and IL-15 receptor blockade prevented chronic rejection. Therefore, antigen and IL-15 pre-sented by dendritic cells play nonredundant key roles in CD8 TRM cell maintenance in settings of antigen per-sistence and inflammation. These findings provide insights that could lead to improved treatment of chronic transplant rejection and autoimmunity.
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