Hogan, Andrew E. (2010) Characterisation of the immunomodulatory properties of human natural killer T cells. PhD thesis, National University of Ireland Maynooth.
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Abstract
Invariant natural killer (iNKT) cells are a small subset of innate cells which express
an invariant T cell receptor and NK surface molecules and recognize glycolipid
antigen presented by CD1. iNKT cells have shown potent anti-tumour properties
when stimulated with the iNKT cell agonist α-galactosylceramide (αGalCer) in
murine models. However iNKT cell based immunotherapies have proved
disappointing in phase I and II clinical trials to date. Humans have a wider
repertoire of CD1-restricted T cells compared to mice. These CD1 restricted T cells
are poorly defined in healthy human blood. In this study we investigated the
reactivity of CD1 in human blood, we identified in healthy donors the majority of
CD1 reactive T cells were identified as iNKT cells. We optimized a method to
readily isolate and expand iNKT from human peripheral blood.
iNKT stimulated with synthetic analogues of αGalCer have shown the potential as
tailored adjuvants for dendritic cell (DC) based immunotherapy. We established a
system to test the immunostimulatory ability of iNKT cell analogues on DC
maturation and function. A novel αGalCer analogue α-S-GalCer stimulated iNKT
cell line to produce a Th1 biased cytokine response and lyse tumour cells. α-SGalCer
stimulated iNKT cells also induced maturation of monocyte derived DC,
and stimulated DC to produce Th1 biased cytokines. Furthermore DC matured by
α-S-GalCer stimulated iNKT cells proliferated allogeneic T cell and induced Th1
cytokine production by the same.
This data shows that the novel iNKT agonist α-S-GalCer stimulates iNKT cell lines
in a Th1 biased fashion and induces DC maturation. Results suggests that α-SGalCer
may possibly be an attractive adjuvant for iNKT/DC based cell
immunotherapy for malignancies and viruses.
Item Type: | Thesis (PhD) |
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Keywords: | Immunomodulatory properties; human natural killer T cells; |
Academic Unit: | Faculty of Science and Engineering > Biology Faculty of Science and Engineering > Research Institutes > Institute of Immunology |
Item ID: | 2332 |
Depositing User: | IR eTheses |
Date Deposited: | 12 Jan 2011 11:40 |
URI: | https://mural.maynoothuniversity.ie/id/eprint/2332 |
Use Licence: | This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here |
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