title: In vivo IL-4 prevents allo-antigen driven CD8+CTL development.
abstract: IL-4 has been shown to suppress acute graft vs. host disease (GVHD) in irradiated hosts. Here we evaluated whether IL-4 suppresses acute GVHD in the un-irradiated parent-into-F1 GVHD model with relevance to renal allograft rejection. IL-4 completely suppressed CD8 CTL when administered with donor cells however this effect was lost if its administration was delayed 3days. IL-4 did not inhibit donor CD8+T cell homing to the host spleen but rather prevented donor CD8+T cell differentiation into CTLs. Studies with IL-4Rα-deficient donor cells or recipient mice demonstrated that IL-4 effects on the host, rather than, or in addition to IL-4 effects on donor cells, were critical for suppression of CTL. Because IL-4 decreased all splenic dendritic cell populations and increased neutrophil and CD8+T cells, IL-4 may suppress donor CD8+CTL by decreasing Ag presentation and/or increasing host myeloid and CD8+T cell suppression of donor T cells.
authors.affiliation: Department of Pathology, Uniformed Services University of Health Sciences, Bethesda, MD 20814, United States. Electronic address: charles.via@usuhs.edu.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Via
authors.affiliation: Department of Pathology, Uniformed Services University of Health Sciences, Bethesda, MD 20814, United States.
authors.forename: Kateryna
authors.initials: K
authors.lastname: Soloviova
authors.affiliation: Department of Pathology, Uniformed Services University of Health Sciences, Bethesda, MD 20814, United States.
authors.forename: Maksym
authors.initials: M
authors.lastname: Puliaiev
authors.affiliation: Department of Pathology, Uniformed Services University of Health Sciences, Bethesda, MD 20814, United States.
authors.forename: Roman
authors.initials: R
authors.lastname: Puliav
authors.affiliation: Department of Pathology, Uniformed Services University of Health Sciences, Bethesda, MD 20814, United States.
authors.forename: Irina
authors.initials: I
authors.lastname: Puliaeva
authors.affiliation: Division of Immunology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, United States; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, United States; Department of Medicine, Cincinnati Veterans Affairs Medical Center, Cincinnati, OH 45220, United States.
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: Morris
authors.affiliation: Division of Immunology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, United States; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, United States; Department of Medicine, Cincinnati Veterans Affairs Medical Center, Cincinnati, OH 45220, United States.
authors.forename: Fred D
authors.initials: FD
authors.lastname: Finkelman
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D006086:Graft vs Host Disease / Q000276:immunology* / Q000628:therapy; D015847:Interleukin-4 / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D000911:Antibodies, Monoclonal; D007519:Isoantigens; D015847:Interleukin-4
keywords: CTL; Cytokine; Graft-vs.-host disease; IL-4; Mouse; T cells