Your browser does not support JavaScript!

Home    Collections    Type of Work    Post-graduate theses  

Post-graduate theses

Search command : Author="Στεφανίδης"  And Author="Κωνσταντίνος"

Current Record: 4679 of 6472

Back to Results Previous page
Next page
Add to Basket
[Add to Basket]
Identifier 000376188
Title Functional analysis of innate immunity receptors in chronic lymphocytic leukemia
Author Vardi, Anna
Author Βαρδή, Άννα
Thesis advisor Παπαδάκη Ελένη
Reviewer Σταματόπουλος, Κώστας
Abstract Background: Mature B cells recognize antigens through the B cell receptor (BCR) in a specific way and through Toll-like receptors (TLRs) and Nod-like receptors (NLRs) in a costimulatory manner. Plenty of evidence supports a role for antigenic stimulation in the natural history of chronic lymphocytic leukemia (CLL). While BCR signaling has extensively been studied, little is known regarding the function of TLRs and NLRs in CLL cells. Design and methods: We used a series of 67 patients, selected with an intentional bias for cases assigned to two different subsets with stereotyped BCRs, namely subsets #1 and #4. We stimulated negatively isolated CLL cells with specific ligands for all TLRs/NLRs found to be expressed in B cells and measured by flow cytometry the upregulation of CD25 and CD86 expression as a marker of NF-κB activation. We compared our findings among CLL subgroups based on IGHV mutational status, IGHV gene usage and BCR stereotypy. Results: TLR9 was functional in practically all cases. TLR1/2, TLR2/6 and NOD2 were functional in most cases with concordant functionality in different cases. TLR7 was functional in fewer cases and responded only to imiquimod, but not loxoribine. Moreover, TLR9 upregulated CD86 expression only in “mutated” CLL cases while TLR7 upregulated CD25 expression only in “unmutated” CLL cases. Finally, TLR1/2, TLR2/6 and NOD2 stimulation had a much stronger effect in CD25/86 upregulation in subset #4 cases when compared to all other “mutated” cases or cases carrying the IGHV4-34 gene in heterogeneous rearrangements. When subset #4 was compared to subset #1, we found that TLR9, TLR1/2, TLR 2/6 and NOD2 stimulation had no effect in CD86 expression in subset #1. Instead, TLR7 stimulation strongly induced CD25 upregulation, in sharp contrast with subset #4. Conclusions: TLRs and NLRs are functional in CLL cells, yet in a heterogeneous fashion. Their stimulation has a pleiotropic effect on the upregulation of costimulatory molecules, depending on the IGHV mutational status. Patterns of TLR/NLR functionality can be recognized among CLL subsets with distinct stereotyped BCRs, offering hints for the nature of the antigenic drive.
Language Greek
Subject Immunity,Innate
Issue date 2010-07-20
Collection   School/Department--School of Medicine--Department of Medicine--Post-graduate theses
  Type of Work--Post-graduate theses
Permanent Link https://elocus.lib.uoc.gr//dlib/d/e/3/metadata-dlib-1351843062-974372-673.tkl Bookmark and Share
Views 229

Digital Documents
No preview available

Download document
View document
Views : 11