Innate and adaptive stimulation of murine diverse NKT cells result in distinct cellular responses

Prabhanshu Tripathi; Saikiran K. Sedimbi; Avadhesh Kumar Singh; Linda Löfbom; Shohreh Issazadeh-Navikas; Siegfried Weiss; Irmgard Förster; Mikael C.I. Karlsson; Ulf Yrlid; Nadir Kadri; Susanna L. Cardell

doi:10.1002/eji.201847647

Innate and adaptive stimulation of murine diverse NKT cells result in distinct cellular responses

Prabhanshu Tripathi, Saikiran K. Sedimbi, Avadhesh Kumar Singh, Linda Löfbom, Shohreh Issazadeh-Navikas, Siegfried Weiss, Irmgard Förster, Mikael C.I. Karlsson, Ulf Yrlid, Nadir Kadri, Susanna L. Cardell^*

^*Corresponding author for this work

2 Citations (Scopus)

18 Downloads (Pure)

Abstract

Natural killer T (NKT) cells recognize glycolipids presented on CD1d. They share features of adaptive T lymphocytes and innate NK cells, and mediate immunoregulatory functions via rapid production of cytokines. Invariant (iNKT) and diverse (dNKT) NKT cell subsets are defined by their TCR. The immunological role of dNKT cells, that do not express the invariant TCRα-chain used by iNKT cells, is less well explored than that of iNKT cells. Here, we investigated signals driving Toll-like receptor (TLR) ligand activation of TCR-transgenic murine dNKT cells. IFN-γ production by dNKT cells required dendritic cells (DC), cell-to-cell contact and presence of TLR ligands. TLR-stimulated DC activated dNKT cells to secrete IFN-γ in a CD1d-, CD80/86- and type I IFN-independent manner. In contrast, a requirement for IL-12p40, and a TLR ligand-selective dependence on IL-18 or IL-15 was observed. TLR ligand/DC stimulation provoked early secretion of pro-inflammatory cytokines by both CD62L⁺ and CD62L⁻ dNKT cells. However, proliferation was limited. In contrast, TCR/co-receptor-mediated activation resulted in proliferation and delayed production of a broader cytokine spectrum preferentially in CD62L⁻ dNKT cells. Thus, innate (TLR ligand/DC) and adaptive (TCR/co-receptor) stimulation of dNKT cells resulted in distinct cellular responses that may contribute differently to the formation of immune memory.

Original language	English
Journal	European Journal of Immunology
Volume	49
Issue number	3
Pages (from-to)	443-453
Number of pages	11
ISSN	0014-2980
DOIs	https://doi.org/10.1002/eji.201847647
Publication status	Published - Mar 2019

Keywords

CD1 molecules
Cytokines
Dendritic cells
NKT cells
Toll like receptors

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Tripathi_et_al-2019-European_Journal_of_ImmunologyFinal published version, 1.19 MBLicence: CC BY

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title = "Innate and adaptive stimulation of murine diverse NKT cells result in distinct cellular responses",

abstract = "Natural killer T (NKT) cells recognize glycolipids presented on CD1d. They share features of adaptive T lymphocytes and innate NK cells, and mediate immunoregulatory functions via rapid production of cytokines. Invariant (iNKT) and diverse (dNKT) NKT cell subsets are defined by their TCR. The immunological role of dNKT cells, that do not express the invariant TCRα-chain used by iNKT cells, is less well explored than that of iNKT cells. Here, we investigated signals driving Toll-like receptor (TLR) ligand activation of TCR-transgenic murine dNKT cells. IFN-γ production by dNKT cells required dendritic cells (DC), cell-to-cell contact and presence of TLR ligands. TLR-stimulated DC activated dNKT cells to secrete IFN-γ in a CD1d-, CD80/86- and type I IFN-independent manner. In contrast, a requirement for IL-12p40, and a TLR ligand-selective dependence on IL-18 or IL-15 was observed. TLR ligand/DC stimulation provoked early secretion of pro-inflammatory cytokines by both CD62L+ and CD62L− dNKT cells. However, proliferation was limited. In contrast, TCR/co-receptor-mediated activation resulted in proliferation and delayed production of a broader cytokine spectrum preferentially in CD62L− dNKT cells. Thus, innate (TLR ligand/DC) and adaptive (TCR/co-receptor) stimulation of dNKT cells resulted in distinct cellular responses that may contribute differently to the formation of immune memory.",

keywords = "CD1 molecules, Cytokines, Dendritic cells, NKT cells, Toll like receptors",

author = "Prabhanshu Tripathi and Sedimbi, {Saikiran K.} and Singh, {Avadhesh Kumar} and Linda L{\"o}fbom and Shohreh Issazadeh-Navikas and Siegfried Weiss and Irmgard F{\"o}rster and Karlsson, {Mikael C.I.} and Ulf Yrlid and Nadir Kadri and Cardell, {Susanna L.}",

year = "2019",

month = mar,

doi = "10.1002/eji.201847647",

language = "English",

volume = "49",

pages = "443--453",

journal = "European Journal of Immunology",

issn = "0014-2980",

publisher = "Wiley - V C H Verlag GmbH & Co. KGaA",

number = "3",

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T1 - Innate and adaptive stimulation of murine diverse NKT cells result in distinct cellular responses

AU - Tripathi, Prabhanshu

AU - Sedimbi, Saikiran K.

AU - Singh, Avadhesh Kumar

AU - Löfbom, Linda

AU - Issazadeh-Navikas, Shohreh

AU - Weiss, Siegfried

AU - Förster, Irmgard

AU - Karlsson, Mikael C.I.

AU - Yrlid, Ulf

AU - Kadri, Nadir

AU - Cardell, Susanna L.

PY - 2019/3

Y1 - 2019/3

N2 - Natural killer T (NKT) cells recognize glycolipids presented on CD1d. They share features of adaptive T lymphocytes and innate NK cells, and mediate immunoregulatory functions via rapid production of cytokines. Invariant (iNKT) and diverse (dNKT) NKT cell subsets are defined by their TCR. The immunological role of dNKT cells, that do not express the invariant TCRα-chain used by iNKT cells, is less well explored than that of iNKT cells. Here, we investigated signals driving Toll-like receptor (TLR) ligand activation of TCR-transgenic murine dNKT cells. IFN-γ production by dNKT cells required dendritic cells (DC), cell-to-cell contact and presence of TLR ligands. TLR-stimulated DC activated dNKT cells to secrete IFN-γ in a CD1d-, CD80/86- and type I IFN-independent manner. In contrast, a requirement for IL-12p40, and a TLR ligand-selective dependence on IL-18 or IL-15 was observed. TLR ligand/DC stimulation provoked early secretion of pro-inflammatory cytokines by both CD62L+ and CD62L− dNKT cells. However, proliferation was limited. In contrast, TCR/co-receptor-mediated activation resulted in proliferation and delayed production of a broader cytokine spectrum preferentially in CD62L− dNKT cells. Thus, innate (TLR ligand/DC) and adaptive (TCR/co-receptor) stimulation of dNKT cells resulted in distinct cellular responses that may contribute differently to the formation of immune memory.

AB - Natural killer T (NKT) cells recognize glycolipids presented on CD1d. They share features of adaptive T lymphocytes and innate NK cells, and mediate immunoregulatory functions via rapid production of cytokines. Invariant (iNKT) and diverse (dNKT) NKT cell subsets are defined by their TCR. The immunological role of dNKT cells, that do not express the invariant TCRα-chain used by iNKT cells, is less well explored than that of iNKT cells. Here, we investigated signals driving Toll-like receptor (TLR) ligand activation of TCR-transgenic murine dNKT cells. IFN-γ production by dNKT cells required dendritic cells (DC), cell-to-cell contact and presence of TLR ligands. TLR-stimulated DC activated dNKT cells to secrete IFN-γ in a CD1d-, CD80/86- and type I IFN-independent manner. In contrast, a requirement for IL-12p40, and a TLR ligand-selective dependence on IL-18 or IL-15 was observed. TLR ligand/DC stimulation provoked early secretion of pro-inflammatory cytokines by both CD62L+ and CD62L− dNKT cells. However, proliferation was limited. In contrast, TCR/co-receptor-mediated activation resulted in proliferation and delayed production of a broader cytokine spectrum preferentially in CD62L− dNKT cells. Thus, innate (TLR ligand/DC) and adaptive (TCR/co-receptor) stimulation of dNKT cells resulted in distinct cellular responses that may contribute differently to the formation of immune memory.

KW - CD1 molecules

KW - Cytokines

KW - Dendritic cells

KW - NKT cells

KW - Toll like receptors

U2 - 10.1002/eji.201847647

DO - 10.1002/eji.201847647

M3 - Journal article

C2 - 30427069

AN - SCOPUS:85058010993

SN - 0014-2980

VL - 49

SP - 443

EP - 453

JO - European Journal of Immunology

JF - European Journal of Immunology

IS - 3

ER -

Innate and adaptive stimulation of murine diverse NKT cells result in distinct cellular responses

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