Resident memory T cells form during persistent antigen exposure leading to allograft rejection.

Autor: Abou-Daya KI; Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.; Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA., Tieu R; Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.; Medical Scientist Training Program, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA., Zhao D; Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.; Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA., Rammal R; Division of Anatomic Pathology, Department of Pathology, American University of Beirut, Beirut, Lebanon., Sacirbegovic F; Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA., Williams AL; Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.; Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA., Shlomchik WD; Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA., Oberbarnscheidt MH; Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. mho6@pitt.edu lakkisf@upmc.edu.; Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA., Lakkis FG; Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. mho6@pitt.edu lakkisf@upmc.edu.; Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Jazyk: angličtina
Zdroj: Science immunology [Sci Immunol] 2021 Mar 19; Vol. 6 (57).
DOI: 10.1126/sciimmunol.abc8122
Abstrakt: Tissue-resident memory T cells (T RM ) contained at sites of previous infection provide local protection against reinfection. Whether they form and function in organ transplants where cognate antigen persists is unclear. This is a key question in transplantation as T cells are detected long term in allografts, but it is not known whether they are exhausted or are functional memory T cells. Using a mouse model of kidney transplantation, we showed that antigen-specific and polyclonal effector T cells differentiated in the graft into T RM and subsequently caused allograft rejection. T RM identity was established by surface phenotype, transcriptional profile, and inability to recirculate in parabiosis and retransplantation experiments. Graft T RM proliferated locally, produced interferon-γ upon restimulation, and their in vivo depletion attenuated rejection. The vast majority of antigen-specific and polyclonal T RM lacked phenotypic and transcriptional exhaustion markers. Single-cell analysis of graft T cells early and late after transplantation identified a transcriptional program associated with transition to the tissue-resident state that could serve as a platform for the discovery of therapeutic targets. Thus, recipient effector T cells differentiate into functional graft T RM that maintain rejection locally. Targeting these T RM could improve renal transplant outcomes.
(Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze: MEDLINE
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