Murine DX5+NKT Cells Display Their Cytotoxic and Proapoptotic Potentials against Colitis-Inducing CD4+CD62Lhigh T Cells through Fas Ligand
Joint Authors
Geissler, Edward K.
Werner, Jens M.
Damian, Michael
Farkas, Stefan A.
Schlitt, Hans J.
Hornung, Matthias
Source
Journal of Immunology Research
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-09-30
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Abstract EN
Introduction.
It has been previously shown that immunoregulatory DX5+NKT cells are able to prevent colitis induced by CD4+CD62Lhigh T lymphocytes in a SCID mouse model.
The aim of this study was to further investigate the underlying mechanism in vitro.
Methods.
CD4+CD62Lhigh and DX5+NKT cells from the spleen of Balb/c mice were isolated first by MACS, followed by FACS sorting and cocultured for up to 96 h.
After polyclonal stimulation with anti-CD3, anti-CD28, and IL-2, proliferation of CD4+CD62Lhigh cells was assessed using a CFSE assay and activity of proapoptotic caspase-3 was determined by intracellular staining and flow cytometry.
Extrinsic apoptotic pathway was blocked using an unconjugated antibody against FasL, and activation of caspase-3 was measured.
Results.
As previously shown in vivo, DX5+NKT cells inhibit proliferation of CD4+CD62Lhigh cells in vitro after 96 h coculture compared to a CD4+CD62Lhigh monoculture (proliferation index: 1.39 ± 0.07 vs.
1.76 ± 0.12; P=0.0079).
The antiproliferative effect of DX5+NKT cells was likely due to an induction of apoptosis in CD4+CD62Lhigh cells as evidenced by increased activation of the proapoptotic caspase-3 after 48 h (38 ± 3% vs.
28 ± 3%; P=0.0451).
Furthermore, DX5+NKT cells after polyclonal stimulation showed an upregulation of FasL on their cell surface (15 ± 2% vs.
2 ± 1%; P=0.0286).
Finally, FasL was blocked on DX5+NKT cells, and therefore, the extrinsic apoptotic pathway abrogated the activation of caspase-3 in CD4+CD62Lhigh cells.
Conclusion.
Collectively, these data confirmed that DX5+NKT cells inhibit proliferation of colitis-inducing CD4+CD62Lhigh cells by induction of apoptosis.
Furthermore, DX5+NKT cells likely mediate their cytotoxic and proapoptotic potentials via FasL, confirming recent reports about iNKT cells.
Further studies will be necessary to evaluate the therapeutical potential of these immunoregulatory cells in patients with colitis.
American Psychological Association (APA)
Werner, Jens M.& Damian, Michael& Farkas, Stefan A.& Schlitt, Hans J.& Geissler, Edward K.& Hornung, Matthias. 2018. Murine DX5+NKT Cells Display Their Cytotoxic and Proapoptotic Potentials against Colitis-Inducing CD4+CD62Lhigh T Cells through Fas Ligand. Journal of Immunology Research،Vol. 2018, no. 2018, pp.1-8.
https://search.emarefa.net/detail/BIM-1193082
Modern Language Association (MLA)
Werner, Jens M.…[et al.]. Murine DX5+NKT Cells Display Their Cytotoxic and Proapoptotic Potentials against Colitis-Inducing CD4+CD62Lhigh T Cells through Fas Ligand. Journal of Immunology Research No. 2018 (2018), pp.1-8.
https://search.emarefa.net/detail/BIM-1193082
American Medical Association (AMA)
Werner, Jens M.& Damian, Michael& Farkas, Stefan A.& Schlitt, Hans J.& Geissler, Edward K.& Hornung, Matthias. Murine DX5+NKT Cells Display Their Cytotoxic and Proapoptotic Potentials against Colitis-Inducing CD4+CD62Lhigh T Cells through Fas Ligand. Journal of Immunology Research. 2018. Vol. 2018, no. 2018, pp.1-8.
https://search.emarefa.net/detail/BIM-1193082
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1193082