| Autor: |
Roger Tieu, Qiang Zeng, Daqiang Zhao, Gang Zhang, Neda Feizi, Priyanka Manandhar, Amanda L. Williams, Benjamin Popp, Michelle A. Wood-Trageser, Anthony J. Demetris, J. Yun Tso, Aaron J. Johnson, Lawrence P. Kane, Khodor I. Abou-Daya, Warren D. Shlomchik, Martin H. Oberbarnscheidt, Fadi G. Lakkis |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Science Immunology. 8 |
| ISSN: |
2470-9468 |
| DOI: |
10.1126/sciimmunol.add8454 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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