Tissue-Specific Distribution of iNKT Cells Impacts Their Cytokine Response

You Jeong Lee; Haiguang Wang; Gabriel J Starrett; Vanessa Phuong; Stephen C Jameson; Kristin A Hogquist

doi:10.1016/j.immuni.2015.06.025

Tissue-Specific Distribution of iNKT Cells Impacts Their Cytokine Response

Immunity. 2015 Sep 15;43(3):566-78. doi: 10.1016/j.immuni.2015.06.025. Epub 2015 Sep 8.

Authors

You Jeong Lee¹, Haiguang Wang¹, Gabriel J Starrett², Vanessa Phuong³, Stephen C Jameson¹, Kristin A Hogquist⁴

Affiliations

¹ The Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
² Biochemistry, Molecular Biology and Biophysics Department, University of Minnesota, Minneapolis, MN 55455, USA.
³ Public Health Studies and Biology, Johns Hopkins University, Baltimore, MD 21218, USA.
⁴ The Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: hogqu001@umn.edu.

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.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Cells, Cultured
Cytokines / immunology*
Cytokines / metabolism
Flow Cytometry
Fluorescent Antibody Technique
Galactosylceramides / immunology
Galactosylceramides / pharmacology
Interferon-gamma / immunology
Interferon-gamma / metabolism
Interleukin-4 / immunology
Interleukin-4 / metabolism
Liver / cytology
Liver / immunology
Liver / metabolism
Lung / cytology
Lung / immunology
Lung / metabolism
Lymph Nodes / cytology
Lymph Nodes / immunology
Lymph Nodes / metabolism
Lymphocyte Activation / drug effects
Lymphocyte Activation / immunology
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred NOD
Mice, Knockout
Mice, Transgenic
Natural Killer T-Cells / classification
Natural Killer T-Cells / immunology*
Natural Killer T-Cells / metabolism
Organ Specificity / drug effects
Organ Specificity / immunology*
Spleen / cytology
Spleen / immunology
Spleen / metabolism
T-Lymphocyte Subsets / cytology
T-Lymphocyte Subsets / immunology*
T-Lymphocyte Subsets / metabolism
Thymocytes / immunology
Thymocytes / metabolism
Thymus Gland / cytology
Thymus Gland / immunology
Thymus Gland / metabolism

Substances

Cytokines
Galactosylceramides
alpha-galactosylceramide
Interleukin-4
Interferon-gamma

Abstract

Publication types

MeSH terms

Substances

Grants and funding