title: IL-18 acts in synergy with IL-7 to promote ex vivo expansion of T lymphoid progenitor cells.
abstract: Although IL-18 has not previously been shown to promote T lymphopoiesis, results obtained via a novel data mining algorithm (global microarray meta-analysis) led us to explore a predicted role for this cytokine in T cell development. IL-18 is a member of the IL-1 cytokine family that has been extensively characterized as a mediator of inflammatory immune responses. To assess a potential role for IL-18 in T cell development, we sort-purified mouse bone marrow-derived common lymphoid progenitor cells, early thymic progenitors (ETPs), and double-negative 2 thymocytes and cultured these populations on OP9-Delta-like 4 stromal layers in the presence or absence of IL-18 and/or IL-7. After 1 wk of culture, IL-18 promoted proliferation and accelerated differentiation of ETPs to the double-negative 3 stage, similar in efficiency to IL-7. IL-18 showed synergy with IL-7 and enhanced proliferation of both the thymus-derived progenitor cells and the bone marrow-derived common lymphoid progenitor cells. The synergistic effect on the ETP population was further characterized and found to correlate with increased surface expression of c-Kit and IL-7 receptors on the IL-18-treated cells. In summary, we successfully validated the global microarray meta-analysis prediction that IL-18 affects T lymphopoiesis and demonstrated that IL-18 can positively impact bone marrow lymphopoiesis and T cell development, presumably via interaction with the c-Kit and IL-7 signaling axis.
authors.affiliation: Department of Surgery, University of Oklahoma School of Community Medicine, Tulsa, OK 74104;
authors.forename: Siva K
authors.initials: SK
authors.lastname: Gandhapudi
authors.affiliation: Department of Surgery, University of Oklahoma School of Community Medicine, Tulsa, OK 74104;
authors.forename: Chibing
authors.initials: C
authors.lastname: Tan
authors.affiliation: Department of Surgery, University of Oklahoma School of Community Medicine, Tulsa, OK 74104;
authors.forename: Julie H
authors.initials: JH
authors.lastname: Marino
authors.affiliation: Department of Surgery, University of Oklahoma School of Community Medicine, Tulsa, OK 74104;
authors.forename: Ashlee A
authors.initials: AA
authors.lastname: Taylor
authors.affiliation: Department of Surgery, University of Oklahoma School of Community Medicine, Tulsa, OK 74104;
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Pack
authors.affiliation: Department of Biological Sciences, Oral Roberts University, Tulsa, OK 74171;
authors.forename: Joel
authors.initials: J
authors.lastname: Gaikwad
authors.affiliation: Department of Surgery, University of Oklahoma School of Community Medicine, Tulsa, OK 74104; Department of Pharmaceutical Sciences, University of Oklahoma College of Pharmacy, Tulsa, OK 74135;
authors.forename: C Justin
authors.initials: CJ
authors.lastname: Van De Wiele
authors.affiliation: Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104; Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104; kent-teague@ouhsc.edu jdwren@gmail.com.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Wren
authors.affiliation: Department of Surgery, University of Oklahoma School of Community Medicine, Tulsa, OK 74104; Department of Pharmaceutical Sciences, University of Oklahoma College of Pharmacy, Tulsa, OK 74135; Department of Psychiatry, University of Oklahoma School of Community Medicine, Tulsa, OK 74104; and Department of Biochemistry and Microbiology, Oklahoma State University Center for the Health Sciences, Tulsa, OK 74107 kent-teague@ouhsc.edu jdwren@gmail.com.
authors.forename: T Kent
authors.identifier: http://orcid.org/0000-0002-4680-5440
authors.initials: TK
authors.lastname: Teague
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology*; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology; D020382:Interleukin-18 / Q000819:agonists / Q000235:genetics / Q000276:immunology*; D015851:Interleukin-7 / Q000819:agonists / Q000235:genetics / Q000276:immunology; D038041:Lymphopoiesis / Q000235:genetics / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D020411:Oligonucleotide Array Sequence Analysis; D054504:Precursor Cells, T-Lymphoid / Q000166:cytology / Q000276:immunology*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
chemical_list: D020382:Interleukin-18; D015851:Interleukin-7; C576410:interleukin-7, mouse; D019009:Proto-Oncogene Proteins c-kit