title: Tissue-Specific Distribution of iNKT Cells Impacts Their Cytokine Response.
abstract: Three subsets of invariant natural killer T (iNKT) cells have been identified, NKT1, NKT2, and NKT17, which produce distinct cytokines when stimulated, but little is known about their localization. Here, we have defined the anatomic localization and systemic distribution of these subsets and measured their cytokine production. Thymic NKT2 cells that produced interleukin-4 (IL-4) at steady state were located in the medulla and conditioned medullary thymocytes. NKT2 cells were abundant in the mesenteric lymph node (LN) of BALB/c mice and produced IL-4 in the T cell zone that conditioned other lymphocytes. Intravenous injection of α-galactosylceramide activated NKT1 cells with vascular access, but not LN or thymic NKT cells, resulting in systemic interferon-γ and IL-4 production, while oral α-galactosylceramide activated NKT2 cells in the mesenteric LN, resulting in local IL-4 release. These findings indicate that the localization of iNKT cells governs their cytokine response both at steady state and upon activation.
authors.affiliation: The Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: You Jeong
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: The Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Haiguang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Biochemistry, Molecular Biology and Biophysics Department, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Gabriel J
authors.initials: GJ
authors.lastname: Starrett
authors.affiliation: Public Health Studies and Biology, Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Phuong
authors.affiliation: The Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Jameson
authors.affiliation: The Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: hogqu001@umn.edu.
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Hogquist
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005699:Galactosylceramides / Q000276:immunology / Q000494:pharmacology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D009928:Organ Specificity / Q000187:drug effects / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D060168:Thymocytes / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D005699:Galactosylceramides; C493154:alpha-galactosylceramide; D015847:Interleukin-4; D007371:Interferon-gamma