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J Immunol. 2016 Mar 15;196(6):2827-37. doi: 10.4049/jimmunol.1500876. Epub 2016 Feb 8.

IL-1 Receptor Signaling on Graft Parenchymal Cells Regulates Memory and De Novo Donor-Reactive CD8 T Cell Responses to Cardiac Allografts.

Author information

1
Department of Immunology, Cleveland Clinic, Cleveland, OH 44195; Division of Immunobiology, Research Institute for Biological Science, Science University of Tokyo, Chiba 278-8510, Japan; Department of Urology, Tokyo Women's Medical University, Tokyo 162-0054, Japan;
2
Department of Immunology, Cleveland Clinic, Cleveland, OH 44195; Department of Urology, Osaka University School of Medicine, Osaka 565-0871, Japan; and.
3
Department of Immunology, Cleveland Clinic, Cleveland, OH 44195;
4
Department of Immunology, Cleveland Clinic, Cleveland, OH 44195; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106.
5
Division of Immunobiology, Research Institute for Biological Science, Science University of Tokyo, Chiba 278-8510, Japan; Department of Urology, Tokyo Women's Medical University, Tokyo 162-0054, Japan;
6
Department of Immunology, Cleveland Clinic, Cleveland, OH 44195; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106 fairchr@ccf.org.

Abstract

Reperfusion of organ allografts induces a potent inflammatory response that directs rapid memory T cell, neutrophil, and macrophage graft infiltration and their activation to express functions mediating graft tissue injury. The role of cardiac allograft IL-1 receptor (IL-1R) signaling in this early inflammation and the downstream primary alloimmune response was investigated. When compared with complete MHC-mismatched wild-type cardiac allografts, IL-1R(-/-) allografts had marked decreases in endogenous memory CD8 T cell and neutrophil infiltration and expression of proinflammatory mediators at early times after transplant, whereas endogenous memory CD4 T cell and macrophage infiltration was not decreased. IL-1R(-/-) allograft recipients also had marked decreases in de novo donor-reactive CD8, but not CD4, T cell development to IFN-γ-producing cells. CD8 T cell-mediated rejection of IL-1R(-/-) cardiac allografts took 3 wk longer than wild-type allografts. Cardiac allografts from reciprocal bone marrow reconstituted IL-1R(-/-)/wild-type chimeric donors indicated that IL-1R signaling on graft nonhematopoietic-derived, but not bone marrow-derived, cells is required for the potent donor-reactive memory and primary CD8 T cell alloimmune responses observed in response to wild-type allografts. These studies implicate IL-1R-mediated signals by allograft parenchymal cells in generating the stimuli-provoking development and elicitation of optimal alloimmune responses to the grafts.

PMID:
26856697
PMCID:
PMC4779689
DOI:
10.4049/jimmunol.1500876
[Indexed for MEDLINE]
Free PMC Article

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