Please use this identifier to cite or link to this item: http://hdl.handle.net/10603/2601
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dc.date.accessioned2011-09-02T10:40:41Z-
dc.date.available2011-09-02T10:40:41Z-
dc.date.issued2011-09-02-
dc.identifier.urihttp://hdl.handle.net/10603/2601-
dc.description.abstractLeishmania donovani, a protozoan parasite, inflicts the fatal disease visceral leishmaniasis, which is characterized by severe immunosuppression. Regulatory T cells (T-reg) mediate immunosuppression and disease progression whereas CD8+ T cells contribute to host protection. Both the disease-promoting and host-protective T cells require CD40-CD40-ligand interaction for their functions suggesting an unknown dual role for CD40 in anti-parasite immune responses. Using Leishmania donovani infection in susceptible BALB/c mice expressing different levels of CD40, we show that CD8+CD40+ T cells function as contra-t-reg cells. Multicolor fluorescence-activated cell sorting analyses, have characterized the target of these contra-t-reg cells. Intriguingly, CD40+CD8+ T cells executed CD40-dependent cytotoxicity against CD4+ T-reg cells. CD40 signaled through Ras, Phosphatidylinositol- 3 kinase (PI-3K) and protein kinase C (PKC) resulting in NF-κB-dependent induction of granzyme B and perforin, the mediators of the cytotoxic function of CD8+ T cells. Adoptive transfer of these cells reduced the Leishmania donovani infection in susceptible BALB/c mice in vivo and reduced Leishmania infection in macrophages in vitro. These CD8+ contra-T-reg cells were apoptosed by IL-10. Thus, CD8+CD40+ T cells function as contra-T-reg cells modulating the course of Leishmania donovani infection, defining a CD40-regulated T-reg/contra-T-reg cellmediated finer regulation of anti-leishmanial immune response.en_US
dc.format.extent96p.en_US
dc.languageEnglishen_US
dc.rightsuniversityen_US
dc.titleRole of CD40 in the regulation of regulatory T cells (T reg.) in Leishmaniasisen_US
dc.creator.researcherMartin, Sunilen_US
dc.subject.keywordBiotechnology, Miceen_US
dc.description.noteReferences p.78-96en_US
dc.contributor.guideSaha, Bhaskaren_US
dc.publisher.placePuneen_US
dc.publisher.universityUniversity of Puneen_US
dc.publisher.institutionNational Centre for Cell Scienceen_US
dc.date.registered0en_US
dc.date.completedMay, 2009en_US
dc.date.awarded2009en_US
dc.format.accompanyingmaterialDVDen_US
dc.type.degreePh.D.en_US
dc.source.inflibnetINFLIBNETen_US
Appears in Departments:National Centre for Cell Science

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01_title.pdfAttached File35.29 kBAdobe PDFView/Open
02_certificate.pdf11.58 kBAdobe PDFView/Open
03_declaration.pdf14.34 kBAdobe PDFView/Open
04_acknowledgement.pdf56.35 kBAdobe PDFView/Open
05_index.pdf11.24 kBAdobe PDFView/Open
06_abbreviations.pdf94.37 kBAdobe PDFView/Open
07_abstract.pdf106.21 kBAdobe PDFView/Open
08_genesis of the thesis.pdf87.96 kBAdobe PDFView/Open
09_chapter 1.pdf1.07 MBAdobe PDFView/Open
10_chapter 2.pdf83.4 kBAdobe PDFView/Open
11_chapter 3.pdf221.81 kBAdobe PDFView/Open
12_chapter 4.pdf1.12 MBAdobe PDFView/Open
13_chapter 5.pdf213.7 kBAdobe PDFView/Open
14_chapter 6.pdf101.98 kBAdobe PDFView/Open
15_publication.pdf81.04 kBAdobe PDFView/Open
16_references.pdf181.27 kBAdobe PDFView/Open


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