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Title: The effect of stimulation with TSLP and KRN7000 on iNKT cell proliferation and cytokine production
Author: Salman, Suhair
ISNI:       0000 0004 5372 3376
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2015
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The effect of stimulation with TSLP and KRN7000 on iNKT cell proliferation and cytokine production (S Salman) iNKT cells are small subset of T lymphocytes that bridge the innate and adaptive immunity. They have the ability to secrete large amount of cytokines upon stimulation with their glycolipid ligand such as αGalactosylceramide or KRN7000 and therefor skew the immune response towards Th1, Th2 or Th17. When in an inflammatory or infectious environment they also are target to signals from other cells that are involved in the immune response. Thymic stromal lymphopoietin (TSLP) is a cytokine that is produced by epithelial cells in allergic diseases and it promotes Th2 response. The hypothesis proposed here is that TSLP may affect iNKT cells directly on TSLPr that may be expressed by these cells and induce a Th2 type cytokines such as IL-4 and IL-13. Also the notion that the addition of TSLP to iNKT cells culture with KRN7000 may stimulate these cells and result in increased proliferation and cytokine production. The first approach to investigate the hypothesis was to optimise the experiment parameters such as the best glycolipid ligand with the optimal concentration and the optimal time point. After that the expression of some markers was investigated especially TSLPr both at day 0 and after 14 days stimulation. Finally the effect of adding TSLP to KRN7000 on iNKT cells (proliferation and cytokine production) in PBMC mixed culture and on enriched iNKT cells and iNKT cell lines were investigated. The results of this work demonstrated that iNKT cells express TSLPr, which is up regulated after stimulation with KRN7000 for 14 days. Furthermore, the addition of TSLP to KRN7000 in iNKT cells in PBMC cultures significantly increases their proliferation in the two healthy donors groups, high and low responders. It also increases IFN-γ production in both groups, IL-13 and IL-17 production in high responders. The cytokine production source was further confirmed to be from iNKT cells after enriching these cells and after using iNKT cells lines. In summary, TSLP and KRN7000 stimulate healthy human iNKT cells and significantly increase their proliferation and cytokine production.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: RZ Other systems of medicine