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Antigen-specific T Cell Responses (antigen-specific t + cell_response)
Selected AbstractsImpaired maturation and function of dendritic cells by mycobacteria through IL-1,EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2006Masahiko Makino Dr. Abstract Dendritic cells (DC) are pivotal for initiation and regulation of innate and adaptive immune responses evoked by vaccination and natural infection. After infection, mycobacterial pathogens first encounter monocytes, which produce pro-inflammatory cytokines, including IL-1,, TNF-, and IL-6. The role of these cytokines in DC maturation remains incompletely understood. Here, we show that maturation of DC from monocytes was impaired by pretreatment of monocytes with low doses of IL-1,. Under these conditions, Mycobacterium leprae -infected DC failed to stimulate antigen-specific T cell responses. Expression of CD86 and CD83 and production of IL-12 in response to lipopolysaccharide and peptidoglycan were diminished. In contrast, these DC functions were not impaired by pretreatment with TNF-,, IL-6 or IL-10. When monocytes were infected with M. bovis Bacillus Calmette-Guérin, and subsequently differentiated to DC, the activity of these DC was suppressed as well. Thus, IL-1, acts at early stages of differentiation of DC and impairs biological functions of DC at later stages. Therefore, production of IL-1, by mycobacteria-infected antigen-presenting cells counteracts effective stimulation of innate and adaptive immune responses. [source] RNA-containing adenovirus/polyethylenimine transfer complexes effectively transduce dendritic cells and induce antigen-specific T cell responsesTHE JOURNAL OF GENE MEDICINE, Issue 4 2004Tatjana C. Gust Abstract Background Dendritic cells (DCs) are the most potent antigen-presenting cells in initiating primary immune responses. Given the unique properties of DCs, gene-modified DCs represent a particularly attractive approach for immunotherapy of diseases such as cancer. Methods Gene-modified DCs were obtained by a receptor-mediated gene delivery system using adenovirus (Ad) particles as ligand and RNA or DNA condensed by polyethylenimine (PEI). In vitro transcribed polyadenylated or non-polyadenylated RNA was used. RNA-transduced DCs were generated expressing chicken ovalbumin (OVA) or chimeric constructs thereof, and compared with DNA-transduced DCs. Results Ad/PEI transfection complexes efficiently delivered RNA into DCs. Such RNA-transduced DCs induced OVA-specific T cell responses more effectively than DNA-transduced DCs. Furthermore, DCs transduced with polyadenylated RNA were more potent in stimulating CD4+ and CD8+ T cell responses than DCs transduced with non-polyadenylated RNA and this was particularly important for CD4+ T cell responses. Conclusions Ad/PEI/RNA transfection is an efficient means for generating RNA-transduced DCs and for stimulating antigen-specific T cell responses. Polyadenylation of RNA enhances CD8+ T cell responses and is essential for CD4+ T cell responses. Copyright © 2004 John Wiley & Sons, Ltd. [source] Increased aeroallergen-specific interleukin-4-producing T cells in asthmatic adultsCLINICAL & EXPERIMENTAL ALLERGY, Issue 12 2002P. Pala Summary Background Asthma, atopy and some forms of respiratory syncytial virus (RSV) disease are thought to be caused by T cells making IL-4 (Th2 cells). However, not all patients with similar patterns of clinical disease have the same underlying pathogenesis and the ability to detect immunopathogenic T cells by examination of the peripheral blood remains in doubt. With the prospect of specific immunotherapy for diseases caused by T cell subsets, it is important to determine whether peripheral blood mononuclear cell (PBMC) reactivity can be used to establish the presence of immunopathogenic responses and therefore to predict therapeutic effects. Objective To detect IL-4 and IFN-, production as markers of Th1 and Th2 responses in the peripheral blood of atopic and asthmatic adults. Methods PBMC from 22 adult asthmatics (18 of whom were atopic) and 21 non-asthmatic volunteers (ten of whom were atopic) were stimulated with cat, birch and house dust mite allergens, human rhinovirus, RSV and recombinant chimaeric F/G protein from RSV in vitro. ELISPOT assays were used to enumerate cells producing IL-4 and IFN-,. Results Asthmatics had a sixfold increase in frequencies of IL-4-producing cells to cat and birch allergen (median values: 37 vs. 7 per million PBMC, P < 0.01 and 20 vs. 3 per million PBMC, P < 0.04, respectively) compared to non-asthmatics. By contrast, non-asthmatic atopics showed no specific increase in antigen-specific IL-4 responses and there was no evident correlation between skin prick test reactivity and ELISPOT results. Atopics had significantly more IFN- ,-producing cells specific for FG than nonatopics. while IFN-, and IL-4 responses to other antigens were not significantly different. Conclusion Enhanced IL-4 responses to non-viral aeroallergens are seen in adults with asthma, while enhanced IFN-, responses to viral antigen FG were seen in atopics. In practical terms, ELISPOT assays for specific cytokines may provide a method that could be used to monitor antigen-specific T cell responses in peripheral blood. [source] | ||||||||||