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Innate and adaptive stimulation of murine diverse NKT cells result in distinct cellular responses
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 immuno...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587840/ https://www.ncbi.nlm.nih.gov/pubmed/30427069 http://dx.doi.org/10.1002/eji.201847647 |
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author | 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. |
author_facet | 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. |
author_sort | Tripathi, Prabhanshu |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6587840 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-65878402019-07-02 Innate and adaptive stimulation of murine diverse NKT cells result in distinct cellular responses 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. Eur J Immunol Molecular immunology and signaling 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. John Wiley and Sons Inc. 2018-12-03 2019-03 /pmc/articles/PMC6587840/ /pubmed/30427069 http://dx.doi.org/10.1002/eji.201847647 Text en © 2018 The Authors. European Journal of Immunology published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Molecular immunology and signaling 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. Innate and adaptive stimulation of murine diverse NKT cells result in distinct cellular responses |
title | Innate and adaptive stimulation of murine diverse NKT cells result in distinct cellular responses |
title_full | Innate and adaptive stimulation of murine diverse NKT cells result in distinct cellular responses |
title_fullStr | Innate and adaptive stimulation of murine diverse NKT cells result in distinct cellular responses |
title_full_unstemmed | Innate and adaptive stimulation of murine diverse NKT cells result in distinct cellular responses |
title_short | Innate and adaptive stimulation of murine diverse NKT cells result in distinct cellular responses |
title_sort | innate and adaptive stimulation of murine diverse nkt cells result in distinct cellular responses |
topic | Molecular immunology and signaling |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587840/ https://www.ncbi.nlm.nih.gov/pubmed/30427069 http://dx.doi.org/10.1002/eji.201847647 |
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