1 |
Rôle des lymphocytes NKT invariants humains dans régulation de la réponse alloimmune / Role Of Human Invariant NKT Lymphocytes In The Regulation Of The Alloimmune ResponseComan, Tereza 11 December 2015 (has links)
La survenue de la maladie du greffon contre l’hôte aiguë (GVHa) après l’allogreffe de cellules souches hématopoïétiques (CSH) reste une source majeure de mortalité et morbidité pour laquelle des avancées thérapeutiques restent indispensables. Les lymphocytes NKT invariants (iNKT) possèdent de multiples propriétés à potentiel immuno-régulateur et anti-tumoral, mais peu de données existent chez l’homme dans le cadre de l’allogreffe de CSH. Nous avons récemment montré qu’une bonne reconstitution en iNKT post greffe ainsi qu’une bonne richesse et capacité d’expansion des iNKT du greffon, notamment du sous type CD4-, étaient corrélés à une moindre survenue de GVHa chez les patients. Ce travail avait pour objectif de déterminer quel sous type de iNKT humain pouvait réguler la réponse allo-immune et ses mécanismes d’action. Dans le modèle murin humanisé de xéno-GVH, chez la souris NSG, nous avons mis en évidence que le sous-type iNKT CD4- humain ,contrairement au sous type CD4+, permettait de diminuer la survenue de GVH et d’améliorer la survie des souris NSG greffées avec des PBMC humains enrichis ou non en lymphocytes iNKT. Nous avons montré de façon concordante, in vivo et in vitro, que les iNKT CD4- humains diminuent le profil Th1 et Th17 des lymphocytes T conventionnels et leur marqueurs d’activation après stimulation allo- et xéno-génique. Par ailleurs, les iNKT CD4- humains induisent la mortalité des cellules dendritiques in vitro et in vivo, contrairement au sous-type iNKT CD4+ qui induit leur maturation. Par contre, les iNKT CD4- n’ont pas d’impact sur les lymphocytes T régulateurs, ni sur la prolifération des T conventionnels. Ils n’altèrent pas non plus la qualité de la prise de greffe des cellules humaines dans la souris NSG. Nous concluons, que contrairement aux iNKT murins, le sous-type iNKT CD4- humain, et non pas CD4+, est capable de diminuer la survenue de xéno-GVH dans le modèle murin NSG par une régulation directe de la réponse immune allogénique. Ces résultats obtenus dans ce modèle préclinique ouvrent la possibilité d’une nouvelle thérapie cellulaire utilisant ces cellules chez l’homme pour prévenir la survenue de GVH aiguë. / The occurrence of acute graft versus host disease (aGVHD) after allogeneic stem cell transplantation (allo-SCT) is a major source of mortality and morbidity and new therapeutic advances are urgently needed. Despite the numerous immunomodulatory properties depicted for the iNKT lymphocytes, there are few studies of these lymphocytes in human allo-SCT and GVHD setting. We previously reported that a higher iNKT reconstitution in patients after allo-SCT and higher graft CD4- iNKT expansion rates, were associated with reduced risk of aGVHD in patients. In this study we aimed to assess a direct immune regulatory role of CD4+ or CD4- iNKT subsets and their mechanisms of action during the allo-immune response. We demonstrated that the human iNKT CD4- subset, but not the CD4+ subset, was associated with reduced xeno-GVHD and prolonged survival of humanized NSG mice infused with human PBSC with or without iNKT cells. We also concomitantly showed, both in vitro and in vivo, that human iNKT CD4- could dampen Th1 and Th17 conventional T cell allo and xeno-responses as well as T cell activation markers. In addition, whereas iNKT CD4+ could stimulate DC maturation, iNKT CD4- induced their apoptosis, in vitro and in vivo. We did not observe any impact on regulatory T cells and conventional T cell proliferation. iNKT CD4- did not impact the engraftment of human cells in NSG mice. We conclude that, by contrast with mice, in humans, the CD4- subset and not their CD4+ counterpart can directly down-regulate the allo-immune response. These results obtained in a robust humanized preclinical xeno-GVH mice model could open new strategies of cellular therapy in the prevention of acute GVHD.
|
2 |
Úloha mutace genu LIF a relativní zastoupení NK buněk, NKT a T lymfocytů ve folikulární tekutině a krvi žen s různou anamnézou neplodnosti / The role of LIF gene mutations and the relative distribution of NK cells, NKT and T lymphocytes in follicular fluid and blood of women with different history of infertilityKřížan, Jiří January 2011 (has links)
Charles University in Prague Faculty of Natural Sciences Summary of Ph.D. thesis The role of LIF gene mutations and the relative distribution of NK cells, NKT and T lymphocytes in follicular fluid and blood of women with different history of infertility Jiří Křížan Prague 2010 1 | P a g e Doctoral degree programs in biomedicine Charles University in Prague and the Academy of Sciences of the Czech Republic Programme: Biomedicine Chairman of the Subject Board: Doc. RNDr. Vladimír Holáň, Dr.Sc. Place of study: Institute of Microbiology, v.v.i., Academy of the Czech Sciences Vídeňská 1083, 142 20 Prague 4 phone: +420 296 442 318 Autor: Mgr. Jiří Křížan Supervisor: RNDr. Petr Šíma, CSc. The dissertation can be found at Dean's Office Faculty of Charles University in Prague 2 | P a g e CONTENTS Contents 2 Summary 3 1. Introduction 5 2. Hypotheses and aims 6 3. Material and methods 7 Material: 7 Methods: 8 4. Results 10 5. Discussion 12 6. Conclusion 15 7. References 16 Bibliography of Autor: 18 1. papers in extenso (thesis background) 18 2. papers in extenso (without regard to thesis) 19 3 | P a g e SUMMARY The aim of the dissertation thesis "The role of LIF gene mutations and the relative distribution of NK cells, NKT, and T lymphocytes in follicular fluid and blood of women with different history of infertility"...
|
3 |
In vitro test buněčné imunitní odpovědi pro diagnostiku Lymeské boreliózy / Lyme borreliosis diagnostics using in vitro cellular immune response testingProkopová, Tereza January 2017 (has links)
Lyme borreliosis is a multisystemic disease affecting skin, joints, heart and central nervous system. The disease is caused by spirochetes of Borrelia burgdorferi sensu lato complex. These bacteria are spread by ticks of Ixodes genus. In 2016 there were almost 4,000 newly infected individuals reported in the Czech Republic. Contemporary serological diagnostics of Lyme borreliosis is not sensitive nor specific enough and does not even correlate with the pathology of the disease in the early or late phases. For the correct diagnosis of the disease it is necessary to detect the pathogen and its genotype. For this reason we had aimed at two goals. Through the digital droplet PCR (ddPCR) method we detected Borrelia-specific DNA and its genotype. The detection limit of borrelial DNA was set on gDNA samples isolated from the tick. Detection threshold for the initial amount of 1 ng of tick gDNA is at the range of 10-17 g of specific borrelial DNA. Borrelia spp. coinfection was detected in 5 out of 12 tested samples. The most frequent type was B. garinii which was detected in 5 samples. On the basis of published sequences for virulent factors we have designed specific primers in conserved regions of the genes flanking their variable segments to be PCR amplified. Gene variability will be monitored through...
|
Page generated in 0.0274 seconds