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

Autor: Tieu R; Medical Scientist Training Program, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA.; Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA., Zeng Q; Nationwide Children's Hospital, Columbus, OH 43205, USA., Zhao D; Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA., Zhang G; Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA., Feizi N; Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA., Manandhar P; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA., Williams AL; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA.; Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA., Popp B; Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.; Division of Transplant Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA., Wood-Trageser MA; Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.; Division of Transplant Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA., Demetris AJ; Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.; Division of Transplant Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA., Tso JY; JN Biosciences, Mountain View, CA 94043, USA., Johnson AJ; Departments of Immunology, Neurology, and Molecular Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA., Kane LP; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA., Abou-Daya KI; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA.; Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA., Shlomchik WD; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA.; Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA., Oberbarnscheidt MH; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA.; Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA., Lakkis FG; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA.; Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Jazyk: angličtina
Zdroj: Science immunology [Sci Immunol] 2023 Apr 21; Vol. 8 (82), pp. eadd8454. Date of Electronic Publication: 2023 Apr 21.
DOI: 10.1126/sciimmunol.add8454
Abstrakt: 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: MEDLINE