IL-10–producing NKT10 cells are a distinct regulatory invariant NKT cell subset
Duygu Sag, … , Mitchell Kronenberg, Gerhard Wingender
Duygu Sag, … , Mitchell Kronenberg, Gerhard Wingender
Published July 25, 2014
Citation Information: J Clin Invest. 2014;124(9):3725-3740. https://doi.org/10.1172/JCI72308.
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Research Article Immunology

IL-10–producing NKT10 cells are a distinct regulatory invariant NKT cell subset

Abstract

Invariant natural killer T (iNKT) cells rapidly produce copious amounts of multiple cytokines after activation, thereby impacting a wide variety of different immune reactions. However, strong activation of iNKT cells with α-galactosylceramide (αGalCer) reportedly induces a hyporeactive state that resembles anergy. In contrast, we determined here that iNKT cells from mice pretreated with αGalCer retain cytotoxic activity and maintain the ability to respond to TCR-dependent as well as TCR-independent cytokine-mediated stimulation. Additionally, αGalCer-pretreated iNKT cells acquired characteristics of regulatory cells, including production and secretion of the immunomodulatory cytokine IL-10. Through the production of IL-10, αGalCer-pretreated iNKT cells impaired antitumor responses and reduced disease in experimental autoimmune encephalomyelitis, a mouse model of autoimmune disease. Furthermore, a subset of iNKT cells with a similar inhibitory phenotype and function were present in mice not exposed to αGalCer and were enriched in mouse adipose tissue and detectable in human PBMCs. These data demonstrate that IL-10–producing iNKT cells with regulatory potential (NKT10 cells) represent a distinct iNKT cell subset.

Authors

Duygu Sag, Petra Krause, Catherine C. Hedrick, Mitchell Kronenberg, Gerhard Wingender

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Figure 5

The phenotype of αGalCer-pretreated iNKT cells is similar to that of Tregs.

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The phenotype of αGalCer-pretreated iNKT cells is similar to that of Tre...
(A and B) Splenic iNKT cells from C57BL/6 control (B6) or C57BL/6 mice injected 1 month earlier with 4 μg αGalCer (B6/αGC) were stained for the indicated surface proteins. Representative data (A) and summary graphs (B) are shown. Numbers in the histograms denote either the geometric mean values or the percentage of positive cells within the depicted gate for the indicated antigens on iNKT cells from mice treated as shown. (C) Expression of CD4 on iNKT cells and CD4+ T cells from spleens from control B6 or B6/αGC mice. Numbers denote the percentage of CD4+ cells (left) and the geometric mean values for CD4 (right) on the cells within the gate depicted in the histogram. (D) Control B6 or B6/αGC mice were either left untreated (Unstimulated) or i.v. injected with 1 μg αGalCer (Stimulated), and the expression of Vα14i TCR was measured on splenic iNKT cells with CD1d-αGalCer tetramers 16 hours later. Numbers in the histograms denote the geometric mean values for the indicated antigens on iNKT cells from mice treated as shown. Summary data for C and D are provided in Supplemental Figure 4, A and B, respectively. Representative data from at least 3 independent experiments are shown in each panel.