IL-10–producing NKT10 cells are a distinct regulatory invariant NKT cell subset
Duygu Sag, Petra Krause, Catherine C. Hedrick, Mitchell Kronenberg, Gerhard Wingender
Duygu Sag, Petra Krause, Catherine C. Hedrick, Mitchell Kronenberg, Gerhard Wingender
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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 11

A subset of Vα24i NKT cells express IL-10.

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A subset of Vα24i NKT cells express IL-10. PBMCs from healthy human dono...
PBMCs from healthy human donors were stimulated with PMA and ionomycin in vitro for 4 hours in the presence of protein transport inhibitors before iNKT cells were analyzed for the indicated markers. (A) Expression of IL-10 and CD4 from 1 representative experiment. Numbers in the dot plots denote the percentage of cells in the respective quadrants. Representative data from 1 of at least 3 independent experiments are shown. (B) Summary graph of the percentage of IL-10+ Vα24i NKT cells (mean: 0.42% ± 0.08%; median: 0.38%). Graph summarizes the results from 6 independent experiments with a total of 20 donors.