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http://hdl.handle.net/10603/2510
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DC Field | Value | Language |
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dc.date.accessioned | 2011-08-30T05:52:29Z | - |
dc.date.available | 2011-08-30T05:52:29Z | - |
dc.date.issued | 2011-08-30 | - |
dc.identifier.uri | http://hdl.handle.net/10603/2510 | - |
dc.description.abstract | Activation of T cells requires signals through antigen-specific T cell receptor and costimulatory molecules such as CD40-ligand (CD40-L). While the use of defined tumor antigens for the induction of protective T cells met with a limited success, CD40-CD40-L interaction that was proposed to induce anti-tumor T cells did not prevent tumor growth completely. Using a model for prostate tumor, a leading cause of tumor-induced mortality in men, it has been shown here that the failure is due to a novel functional dichotomy of CD40 whereby it self-limits its anti-tumor functions by inducing interleukin-10. Interleukin-10 prevents the CD40-induced cytotoxic T cells (CTL) and TNF-α and interleukin-12 production, Th1 skewing and tumor regression. Priming mice with tumor lysate-pulsed interleukin-10-deficient DCs or wild-type DC plus antiinterleukin- 10 antibody establishes anti-tumor memory T cells that can transfer the protection into syngenic nude mice. Infusion of antigen-pulsed interleukin-10-deficient but not wild-type DCs back into syngenic mice results in successful therapeutic autovaccination. Having addressed a novel functional dichotomy of CD40 whereby it induces anti-tumor T cells and a pro-tumor cytokine, interleukin-10, the underlying mechanism for the observed duality in CD40 function has been deciphered using mice expressing different levels of CD40 or CD40-L and different doses of anti-CD40 antibody. Using mice expressing different levels of CD40 or CD40-L and different doses of anti-CD40 antibody, it has been shown that greater the T cell CD40-L expression less is the tumor growth and host-protective is the anti-tumor T cell response. Lower CD40-L expression induced higher IL-10 production, and a parallel IL-4-dominated response, IL- 10-sensitive effector T cells and suppressed tumor-regressing T cells. Thus the results demonstrate that a dose-dependent cross-linking of a costimulatory molecule dictates the functional phenotype of the elicited effector T cell response. The T cell costimulation is a continuum of a function that induces not only graded T cell responses but also two counteracting responses at two extremes. | en_US |
dc.format.extent | 157p. | en_US |
dc.language | English | en_US |
dc.rights | university | en_US |
dc.title | Role of CD 40 in the regulation of anti tumor immune response | en_US |
dc.creator.researcher | Murugaiyan, G | en_US |
dc.subject.keyword | Biotechnology, Tumor | en_US |
dc.description.note | Abstract includes, References p.107-155 | en_US |
dc.contributor.guide | Saha, Bhaskar | en_US |
dc.publisher.place | Pune | en_US |
dc.publisher.university | University of Pune | en_US |
dc.publisher.institution | National Centre for Cell Science | en_US |
dc.date.registered | 0 | en_US |
dc.date.completed | September, 2006 | en_US |
dc.date.awarded | 2006 | en_US |
dc.format.accompanyingmaterial | DVD | en_US |
dc.type.degree | Ph.D. | en_US |
dc.source.inflibnet | INFLIBNET | en_US |
Appears in Departments: | National Centre for Cell Science |
Files in This Item:
File | Description | Size | Format | |
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01_title.pdf | Attached File | 72.75 kB | Adobe PDF | View/Open |
02_certificate.pdf | 45.28 kB | Adobe PDF | View/Open | |
03_declaration.pdf | 77.33 kB | Adobe PDF | View/Open | |
04_acknowledgement.pdf | 48.28 kB | Adobe PDF | View/Open | |
05_index.pdf | 63.15 kB | Adobe PDF | View/Open | |
06_abbreviations.pdf | 87.83 kB | Adobe PDF | View/Open | |
07_abstract.pdf | 150.88 kB | Adobe PDF | View/Open | |
08_chapter 1.pdf | 1.32 MB | Adobe PDF | View/Open | |
09_chapter 2.pdf | 150.91 kB | Adobe PDF | View/Open | |
10_chapter 3.pdf | 273.15 kB | Adobe PDF | View/Open | |
11_chapter 4.pdf | 591.47 kB | Adobe PDF | View/Open | |
12_chapter 5.pdf | 269.57 kB | Adobe PDF | View/Open | |
13_references.pdf | 325.08 kB | Adobe PDF | View/Open | |
14_publications.pdf | 914.31 kB | Adobe PDF | View/Open |
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