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

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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 languageEnglish
JournalEuropean Journal of Immunology
Volume49
Issue number3
Pages (from-to)443-453
Number of pages11
ISSN0014-2980
DOIs
Publication statusPublished - 2019

Keywords

  • CD1 molecules
  • Cytokines
  • Dendritic cells
  • NKT cells
  • Toll like receptors

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