FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4230442380> ?p ?o ?g. }

• W4230442380 endingPage "803" @default.
• W4230442380 startingPage "803" @default.
• W4230442380 abstract "Abstract Abstract 803 Introduction: The development of B cell chronic lymphocytic leukaemia (CLL) involves antigenic selection of the B cell clone, as evidenced by a skewed BCR repertoire found in CLL cells, as well as continuing BCR signaling detected in subgroups of CLL. T cell involvement in the maintenance of the malignant clone is also suggested by a number of evidential lines, such as the severe skewing of T cell subsets in CLL and the presence of relevant numbers of CD4 cells in the so-called “proliferation centers” in lymph nodes. However, neither clonal nor immunologic identities of these T cells have been sufficiently determined. Recently, we have shown in Tcl1 transgenic mice that CLL clones were able to directly drive changes in the T cell repertoire, resulting in relatively fast skewing in subset distribution (similar to that observed in human CLL) as well as a clonal selection of T cells, both in spontaneously developing CLL in the model, as well as in immunocompetent congenic recipient mice in experiments transplanting established murine CLL. Methods: To establish evidence for similar interactions in human CLL, we collected a descriptive database determining patterns of T cell diversity in CLL patient blood. We analyzed T cells from 53 previously-untreated CLL patients established TCR V beta clonality and frequency based on CDR3 length polymorphism in sorted CD4 cells and, in a confirmatory subset, based on TCR V gene-specific flow cytometry. CLL samples were also investigated regarding the BCR VH gene usage, mutation status and clinical and prognostic parameters. Results: BCR analysis confirmed antigenic selection in our patient set with 6 IgVH genes accounting for > 50% of the cases. Stereotyped CDR3 regions were common and one third of the patients showed unmutatetd IgVH gene sequence. Analysing 20 TCR genes by PCR spectratyping, the TCR CDR3 size distribution pattern revealed a relevant frequency of oligoclonal/monoclonal CD4 T cells in CLL samples. While a number of patients showed completely polyclonal patterns in all their TCR CDR3 regions, others showed either single or multiple clonal TCR families. In corresponding flow cytometric analyses clonal T cells could make up to 48% of total CD4 cells in a given patient. In patients with longitudinal samples we found relevant stability of these TCR patterns over time. By comparing the data from the TCR clonality database with our BCR dataset we established that these clonal patterns significantly, but not exclusively, clustered in unmutated patient samples. Overall we found no strong association with any specific IgVH gene, but intriguingly, in some patients a specific clonal TCR corresponded to a stereotyped BCR receptor. In fact in two patient pairs with identical IgVH rearrangements we found corresponding TCR clones that showed sequence identity between the CD4 T cell clones derived from the other patient. In addition in both pairs we found a shared HLA DR and DQ haplotype. These data strongly suggests that there may be an important link between the antigenic selection on the B-CLL clone and the selection of certain TCR clones, thus for the first time postulating an antigentic identity of the CLL-associated T cells. This proposed identity, however, currently remains unclear. Finally, we tested for an influence of T cell clonality on clinical behaviour of CLL disease in the patients. We could intentify the presence of more than one clonal TCR family as a significant predictor of a short treatment-free interval (p=0.03). This was true for both, patients with mutated and unmutated IgVH receptors, although it remained a trend in the latter. Conclusion: Our results imply that a restricted CD4 T cell diversity may be important for CLL progression and that an as of yet still undefined antigenic drive for T cells may be important for this. This may help to define specific monoclonal CD4 T cells as a promising novel target for future therapeutic intervention. Disclosures: No relevant conflicts of interest to declare." @default.
• W4230442380 created "2022-05-11" @default.
• W4230442380 creator A5011192385 @default.
• W4230442380 creator A5028047744 @default.
• W4230442380 creator A5039762705 @default.
• W4230442380 creator A5039994927 @default.
• W4230442380 creator A5045993698 @default.
• W4230442380 creator A5061017636 @default.
• W4230442380 creator A5070000759 @default.
• W4230442380 creator A5070621037 @default.
• W4230442380 date "2011-11-18" @default.
• W4230442380 modified "2023-10-17" @default.
• W4230442380 title "Clonal Diversity of the T Cell Repertoire Predicts Disease Progression in Chronic Lymphocytic Leukaemia" @default.
• W4230442380 doi "https://doi.org/10.1182/blood.v118.21.803.803" @default.
• W4230442380 hasPublicationYear "2011" @default.
• W4230442380 type Work @default.
• W4230442380 citedByCount "0" @default.
• W4230442380 crossrefType "journal-article" @default.
• W4230442380 hasAuthorship W4230442380A5011192385 @default.
• W4230442380 hasAuthorship W4230442380A5028047744 @default.
• W4230442380 hasAuthorship W4230442380A5039762705 @default.
• W4230442380 hasAuthorship W4230442380A5039994927 @default.
• W4230442380 hasAuthorship W4230442380A5045993698 @default.
• W4230442380 hasAuthorship W4230442380A5061017636 @default.
• W4230442380 hasAuthorship W4230442380A5070000759 @default.
• W4230442380 hasAuthorship W4230442380A5070621037 @default.
• W4230442380 hasConcept C104317684 @default.
• W4230442380 hasConcept C121332964 @default.
• W4230442380 hasConcept C19317047 @default.
• W4230442380 hasConcept C203014093 @default.
• W4230442380 hasConcept C24890656 @default.
• W4230442380 hasConcept C2776090121 @default.
• W4230442380 hasConcept C2777868816 @default.
• W4230442380 hasConcept C2777938653 @default.
• W4230442380 hasConcept C2778461978 @default.
• W4230442380 hasConcept C2778473898 @default.
• W4230442380 hasConcept C43907098 @default.
• W4230442380 hasConcept C54355233 @default.
• W4230442380 hasConcept C81089528 @default.
• W4230442380 hasConcept C86803240 @default.
• W4230442380 hasConcept C8891405 @default.
• W4230442380 hasConceptScore W4230442380C104317684 @default.
• W4230442380 hasConceptScore W4230442380C121332964 @default.
• W4230442380 hasConceptScore W4230442380C19317047 @default.
• W4230442380 hasConceptScore W4230442380C203014093 @default.
• W4230442380 hasConceptScore W4230442380C24890656 @default.
• W4230442380 hasConceptScore W4230442380C2776090121 @default.
• W4230442380 hasConceptScore W4230442380C2777868816 @default.
• W4230442380 hasConceptScore W4230442380C2777938653 @default.
• W4230442380 hasConceptScore W4230442380C2778461978 @default.
• W4230442380 hasConceptScore W4230442380C2778473898 @default.
• W4230442380 hasConceptScore W4230442380C43907098 @default.
• W4230442380 hasConceptScore W4230442380C54355233 @default.
• W4230442380 hasConceptScore W4230442380C81089528 @default.
• W4230442380 hasConceptScore W4230442380C86803240 @default.
• W4230442380 hasConceptScore W4230442380C8891405 @default.
• W4230442380 hasIssue "21" @default.
• W4230442380 hasLocation W42304423801 @default.
• W4230442380 hasOpenAccess W4230442380 @default.
• W4230442380 hasPrimaryLocation W42304423801 @default.
• W4230442380 hasRelatedWork W14431212 @default.
• W4230442380 hasRelatedWork W18630108 @default.
• W4230442380 hasRelatedWork W20237428 @default.
• W4230442380 hasRelatedWork W2522140 @default.
• W4230442380 hasRelatedWork W29804434 @default.
• W4230442380 hasRelatedWork W30665812 @default.
• W4230442380 hasRelatedWork W30793397 @default.
• W4230442380 hasRelatedWork W39126919 @default.
• W4230442380 hasRelatedWork W6085161 @default.
• W4230442380 hasRelatedWork W8161482 @default.
• W4230442380 hasVolume "118" @default.
• W4230442380 isParatext "false" @default.
• W4230442380 isRetracted "false" @default.
• W4230442380 workType "article" @default.