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

• Published in: European journal of immunology 2019-03, Vol.49 (3), p.443-453
• Main Authors: Tripathi, Prabhanshu, Sedimbi, Saikiran K., Singh, Avadhesh Kumar, Löfbom, Linda, Issazadeh‐Navikas, Shohreh, Weiss, Siegfried, Förster, Irmgard, Karlsson, Mikael C. I., Yrlid, Ulf, Kadri, Nadir, Cardell, Susanna L.
• Format: Article
• Language: English
• Subjects: Activation; Adaptive Immunity - immunology; Animals; Antigens, CD1d - genetics; Antigens, CD1d - immunology; Antigens, CD1d - metabolism; Basic; CD1 molecules; CD1d antigen; CD80 antigen; Cell proliferation; Cell Proliferation - genetics; Cells, Cultured; Cytokines; Cytokines - immunology; Cytokines - metabolism; Dendritic cells; Dependence; Glycolipids; Immunity, Cellular - immunology; Immunity, Innate - immunology; Immunologi inom det medicinska området; Immunological memory; Immunology; Immunology in the medical area; Immunoregulation; Inflammation; Interferon; Invariants; L-selectin; Ligands; Lymphocytes; Lymphocytes - immunology; Lymphocytes - metabolism; Lymphocytes T; Medicin och hälsovetenskap; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Molecular immunology and signaling; Natural killer cells; Natural Killer T-Cells - immunology; Natural Killer T-Cells - metabolism; NKT cells; Secretion; Stimulation; T cell receptors; Toll like receptors; Toll-Like Receptors - immunology; Toll-Like Receptors - metabolism
• ISSN: 0014-2980; 1521-4141; 1521-4141
• DOI: 10.1002/eji.201847647

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. Activation of dNKT cells by DC and TLR ligands depends on cytokines and CD40, but not CD1d ‐ TCR interaction, inducing early IFN‐γ but low proliferation. In contrast, TCR ‐ co‐receptor stimulation results in robust proliferation and late secretion of more cytokines. Thus, activation mode may influence memory formation.