Tissue-resident memory T cell maintenance during antigen persistence requires both cognate antigen and interleukin-15
Inflammation
Interleukin-15
Memory T Cells
Humans
Antigens
CD8-Positive T-Lymphocytes
3. Good health
DOI:
10.1126/sciimmunol.add8454
Publication Date:
2023-04-21T17:58:06Z
AUTHORS (17)
ABSTRACT
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.
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