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

• Published in: Science immunology Vol. 8; no. 82; p. eadd8454
• Main Authors: Tieu, Roger, Zeng, Qiang, Zhao, Daqiang, Zhang, Gang, Feizi, Neda, Manandhar, Priyanka, Williams, Amanda L, Popp, Benjamin, Wood-Trageser, Michelle A, Demetris, Anthony J, Tso, J Yun, Johnson, Aaron J, Kane, Lawrence P, Abou-Daya, Khodor I, Shlomchik, Warren D, Oberbarnscheidt, Martin H, Lakkis, Fadi G
• Format: Journal Article
• Language: English
• Published: United States 21.04.2023
• Subjects: Antigens; CD8-Positive T-Lymphocytes; Humans; Inflammation; Interleukin-15; Memory T Cells
• ISSN: 2470-9468
• DOI: 10.1126/sciimmunol.add8454

Our understanding of tissue-resident memory T (T ) 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 cells in the context of chronic antigen persistence and inflammation. We investigated factors that underlie T maintenance in a kidney transplantation model in which T cells drive rejection. In contrast to acute infection, we found that T 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 cells were established was sufficient to disrupt T maintenance and reduce allograft pathology. Likewise, removal of IL-15 transpresentation or of the IL-15 receptor on T cells during T maintenance led to a decline in T 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 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.