title: Skin allograft rejection is suppressed in mice lacking the antiviral enzyme, 2',5'-oligoadenylate-dependent RNase L.
abstract: The 2-5A/RNase L system is a regulated RNA decay pathway that mediates some of the antiviral and tumor suppressor activities of the interferons. Previously, we demonstrated that RNase L-null mice have increased susceptibility to viral infections and are partially deficient in induced and spontaneous apoptosis. To determine if RNase L functions in cellular, as well as innate, immunity, skin allograft rejection and contact hypersensitivity (CHS) experiments were performed in RNase L+/+ and RNase L-/- mice. Although no consistent alterations in CHS were found, we did observe a delay of 5 days in the acute rejection of class II major histocompatibility complex (MHC) disparate skin allografts in mice lacking RNase L. Accordingly, histologic examinations of the allografts harvested from RNase L-/- mice revealed a dramatic reduction in inflammatory infiltrates, suggesting a delay in T-cell priming or a deficiency in immune cell trafficking. Results consistent with a proinflammatory role for RNase L extend the known functions of the 2-5A/RNase L system beyond innate immunity into some, but not all, types of cellular immunity.
authors.affiliation: Department of Cancer Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Ohio 44195, USA. silverr@ccf.org
authors.forename: Robert H
authors.initials: RH
authors.lastname: Silverman
authors.forename: Aimin
authors.initials: A
authors.lastname: Zhou
authors.forename: Michael B
authors.initials: MB
authors.lastname: Auerbach
authors.forename: Danielle
authors.initials: D
authors.lastname: Kish
authors.forename: Anton
authors.initials: A
authors.lastname: Gorbachev
authors.forename: Robert L
authors.initials: RL
authors.lastname: Fairchild
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004722:Endoribonucleases / Q000502:physiology*; D006084:Graft Rejection / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D016038:Skin Transplantation / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease