Antigen-specific effector CD8 T cells regulate allergic responses via IFN-γ and dendritic cell function - 31/05/12
Corresponding author: David M. Kemeny, PhD, FRCPath, Immunology Programme, Centre for Life Sciences, National University of Singapore #03-05, 28 Medical Dr, Singapore 117456.Abstract |
Background |
Previous studies have shown that CD8 T cells can both prevent and cause allergic responses. However, the underlying mechanisms remain to be elucidated.
Objective |
We aim to investigate the potential of CD8 T cells with different IFN-γ expressions to modulate the elicitation of allergic inflammation following ovalbumin (OVA) challenge and investigate the underlying mechanisms.
Methods |
To study the role of IFN-γ in the effect of CD8 T cells, effector CD8 T cells from CD8 OVA transgenic (OT-I) mice and IFN-γ−/−OT-I mice were transferred to OVA-sensitized mice the day before 3 challenges with OVA. The effect on lung dendritic cells (DCs) exerted by CD8 T cells was studied with ex vivo culture of sorted DCs from treatment mice with CD4 T cells.
Results |
Effector OT-I, but not IFN-γ−/−OT-I CD8 T cells, attenuated eosinophilia and mucus secretion in the lungs of sensitized mice in an antigen-specific manner. Effector IFN-γ−/−OT-I CD8 T cells displayed a Tc2-/Tc17-biased phenotype with weaker cytotoxicity and were able to both induce and exacerbate eosinophilia as well as neutrophilia. OT-I CD8 T cells increased the ability of lung CD11b+CD103− DCs to both prime the differentiation of naive OVA-specific CD4 T cells toward a TH1 phenotype and enhance IFN-γ production by antigen-experienced lung CD4 T cells.
Conclusion |
Effector CD8 T cells attenuate pulmonary inflammation and alter the ability of DCs within the allergic lung to polarize T cells to a TH1 phenotype during a TH2 response. In the absence of IFN-γ, CD8 T cells assume a Tc2-/Tc17-biased phenotype and potentiate inflammation.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, OT-I, IFN-γ−/−OT-I, CD8 T cells, effector, IFN-γ, eosinophils, CD11b+CD103−DC, TH1
Abbreviations used : AHR, BAL, DC, OVA
Plan
| This work was supported by the Biomedical Research Council (grant no. BMRC 05/1/21/19/41). Y.T. was supported by an NGS scholarship. D.M.K. is supported by the National Research Foundation HUJ-CREATE programme on Cellular and Molecular Mechanisms of Inflammation. |
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| Disclosure of potential conflict of interest: D. M. Kemeny is on the Johnson & Johnson Scientific Advisory Committee. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 129 - N° 6
P. 1611 - juin 2012 Retour au numéro
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