The effects of the balance of Type I and Type II NKT cells on CD8 T cells and tumour therapy.

Dora Chan (2010). The effects of the balance of Type I and Type II NKT cells on CD8 T cells and tumour therapy. PhD Thesis, Diamantina Institute for Cancer, Immunology and Metabolic Medicine, The University of Queensland.

       
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s40072638_PhD_abstract.pdf s40072638 PhD Abstract application/pdf 70.45KB 2
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Author Dora Chan
Thesis Title The effects of the balance of Type I and Type II NKT cells on CD8 T cells and tumour therapy.
School, Centre or Institute Diamantina Institute for Cancer, Immunology and Metabolic Medicine
Institution The University of Queensland
Publication date 2010-09
Thesis type PhD Thesis
Supervisor Dr Graham Leggatt
Prof Ian Frazer
Total pages 183
Total colour pages 25
Total black and white pages 158
Subjects 11 Medical and Health Sciences
Abstract/Summary There is convincing evidence that NKT cells are a critical link between the innate and adaptive arms of the immune response in a range of diseases, including cancer. We are currently investigating specifically the cellular interactions between NKT cells and CD8+ effector T cells. From in vivo mouse experiments we have shown that both Type I invariant NKT cells and CD8 T cells are required for controlling the growth of early stage tumours. In vivo tumour protection experiments, utilizing mice deficient in different subsets of NKT cells (Jα18KO and CD1dKO mice) however, indicate that a suppressive NKT cell population (Type II NKT cells) is capable of regulating antigen-specific anti-tumour responses in the absence of Type I NKT cells. Collectively, these data suggest that the balance of different subtypes of NKT cells may have important roles in the promotion or prevention of CD8 T cell mediated anti-tumour immune responses. In order to dissect the influences of activated Type I and Type II NKT cells on the functionality of CD8 T cells specific for the Human Papillomavirus Type 16 (HPV16) E7 protein, the activation and function of CD8 T cells were investigated in three mouse models: Wild type C57 (both Type I and Type II NKT cells coexist), Jα18KO mice (only Type II NKT cells are present), and CD1dKO mice (lack both Type I and Type II NKT cells). We have found that there are no significant differences in cell proliferation, in vivo killing of target cells, or activation markers of CD8 T cells between C57 and Jα18KO mice. However, CD8 T cells of CD1dKO mice are functionally enhanced compared to C57 and Jα18KO mice. In addition, the draining lymph node cells of immunized CD1dKO mice consistently produce higher Th1 cytokines compared to the draining lymph nodes of immunized C57 and Jα18KO mice. Adoptive transfer of draining lymph node cells of immunized C57, Jα18KO, and CD1dKO mice into tumour-bearing recipient mice showed that the proportion of CD8 T cells from C57 mice is slightly higher at the tumour site compared to Jα18KO mice. However, the chemokine receptor profiles of CD8 T cells from immunized C57, Jα18KO, and CD1dKO mice were similar. The proportion and number of myeloid derived suppressor cells (CD11b+Gr1+) and CD4 regulatory T cells were similar between C57, Jα18KO, and CD1dKO mice. The activation phenotype of dendritic cells from immunized C57, Jα18KO, and CD1dKO mice were also examined. No differences were observed in terms of the expression of co-stimulatory molecules such as CD40 and CD80. These results contribute to the understanding of how different NKT cell subsets regulate components of the cellular adaptive immune response to tumours, which may lead to more targeted and effective immune therapies for cancer in the future.
Keyword NKT cells
CD8 T cells
Tumour
Additional Notes Coloured pages (total 25 pages): Pages 69, 73, 76, 78, 80, 82, 84, 87, 89, 91, 93, 109, 111, 112, 115, 117, 123, 132, 133, 135, 136, 138, 139, 140, 144 Landscape pages (total 1 page): Page 112

 
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Created: Wed, 09 Feb 2011, 11:41:01 EST by Ms Dora Chan on behalf of Library - Information Access Service