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master's thesis
UTJECAJ INHIBITORA PROTEINA BCL-2 OBITELJI NA STVARANJE MEMORIJSKIH CD8 LIMFOCITA T
Rijeka: University of Rijeka, Faculty of Medicine, 2021. urn:nbn:hr:184:707942
Majnarić, Dora
University of Rijeka
Faculty of Medicine
Department of Histology and Embryology

Institutional repository: Repository of the University of Rijeka, Faculty of Medicine

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Majnarić, D. (2021). UTJECAJ INHIBITORA PROTEINA BCL-2 OBITELJI NA STVARANJE MEMORIJSKIH CD8 LIMFOCITA T (Master's thesis). Rijeka: University of Rijeka, Faculty of Medicine. Retrieved from https://urn.nsk.hr/urn:nbn:hr:184:707942

Majnarić, Dora. "UTJECAJ INHIBITORA PROTEINA BCL-2 OBITELJI NA STVARANJE MEMORIJSKIH CD8 LIMFOCITA T." Master's thesis, University of Rijeka, Faculty of Medicine, 2021. https://urn.nsk.hr/urn:nbn:hr:184:707942

Majnarić, Dora. "UTJECAJ INHIBITORA PROTEINA BCL-2 OBITELJI NA STVARANJE MEMORIJSKIH CD8 LIMFOCITA T." Master's thesis, University of Rijeka, Faculty of Medicine, 2021. https://urn.nsk.hr/urn:nbn:hr:184:707942

Majnarić, D. (2021). 'UTJECAJ INHIBITORA PROTEINA BCL-2 OBITELJI NA STVARANJE MEMORIJSKIH CD8 LIMFOCITA T', Master's thesis, University of Rijeka, Faculty of Medicine, accessed 26 November 2024, https://urn.nsk.hr/urn:nbn:hr:184:707942

Majnarić D. UTJECAJ INHIBITORA PROTEINA BCL-2 OBITELJI NA STVARANJE MEMORIJSKIH CD8 LIMFOCITA T [Master's thesis]. Rijeka: University of Rijeka, Faculty of Medicine; 2021 [cited 2024 November 26] Available at: https://urn.nsk.hr/urn:nbn:hr:184:707942

D. Majnarić, "UTJECAJ INHIBITORA PROTEINA BCL-2 OBITELJI NA STVARANJE MEMORIJSKIH CD8 LIMFOCITA T", Master's thesis, University of Rijeka, Faculty of Medicine, Rijeka, 2021. Available at: https://urn.nsk.hr/urn:nbn:hr:184:707942

Metadata
TitleUTJECAJ INHIBITORA PROTEINA BCL-2 OBITELJI NA STVARANJE MEMORIJSKIH CD8 LIMFOCITA T
Title (english)The impact of BCL-2 protein family inhibitors on the formation of memory CD8 T cells
AuthorDora Majnarić
MentorFelix Martinus Wensveen (mentor)
MentorInga Kavazović (komentor)
Committee memberBojan Polić (predsjednik povjerenstva)
GranterUniversity of Rijeka
Faculty of Medicine
(Department of Histology and Embryology)
Rijeka
Defense date and country2021-07-09, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Basic Medical Sciences
Immunology
Abstract
Imunost posredovana CD8 limfocitima T ima presudnu ulogu u zaštiti našeg tijela od infekcija uzrokovanih unutarstaničnih patogenima. Nakon uklanjanja uzročnika infekcije, većina antigen-specifičnih CD8 limfocita T odumire apoptozom, ostavljajući za sobom malu populaciju dugovječnih memorijskih stanica. Još uvijek nisu razjašnjeni mehanizmi koji reguliraju diferencijaciju CD8 limfocita T. Nedavna istraživanja ukazala su na važnost intenziteta signala na T-stanični receptor i ispoljavanja proteina BCL-2 obitelji u procesu diferencijacije u memorijske stanice. Ovim istraživanjem utvrđen je utjecaj specifičnih inhibitora proteina BCL-2 obitelji na stvaranje memorijskih CD8 limfocita T in vitro. Najprije je uspostavljen i validiran in vitro model korištenjem čiste populacije CD8 limfocita T dobivene pomoću magnetske separacije stanica iz slezene transgeničnih OT-1 miševa. Stanice su stimulirane s peptidima različitog afiniteta za T-stanični receptor, SIINFEKL (N4) i SIIQFEKL (Q4) te s inhibitorom BAI1 (inhibitor BAX molekule) i ABT-199 (inhibitor BCL-2 molekule). Fenotipske i funkcionalne karakteristike te postotak preživljenja stanica su praćene pomoću protočne citometrije koristeći specifična protutijela. CD8 limfociti T stimulirani s peptidom visokog afiniteta (N4) bolje poprimaju efektorski fenotip (ispoljavaju više razine CD25, CD69 i CD44), dok stanice stimulirane s peptidom nižeg afiniteta (Q4) brže poprimaju memorijski fenotip (ispoljavaju više razine CD127, CCR7 i CD62L). Inhibicija molekule BAX, odnosno inkubacija stanica s BAI1 inhibitorom nije imala utjecaj na stvaranje memorijskih CD8 limfocita T, bez obzira jesu li stanice stimulirane N4 ili Q4 peptidom. Inhibicija molekule BCL-2 (inhibitor ABT-199) je rezultirala smanjenim preživljenjem stanica nižeg afiniteta (Q4) u prvim danima nakon stimulacije pri većim koncentracijama inhibitora u odnosu na stanice višeg afiniteta (N4).
Abstract (english)
Immunity mediated by CD8 T cells plays a crucial role in protecting our body from infections caused by intracellular pathogens. After removal of the infectious agent, most antigen-specific CD8 T cells die by apoptosis, leaving behind a small population of long-lived memory cells. The mechanisms that regulate CD8 T cell differentiation have not yet been elucidated. Recent studies indicate the importance of T-cell receptor signal intensity and BCL-2 protein family expression in the process of differentiation into memory cells. Here, we determined the effect of specific BCL-2 protein family inhibitors on the formation of memory CD8 T cells in vitro. First, an in vitro model was established and validated using a pure population of CD8 T lymphocytes obtained by magnetic separation of splenocytes from OT-1 mice. Cells were stimulated with peptides of different affinity for the T-cell receptor, SIINFEKL (N4) and SIIQFEKL (Q4) and with inhibitors - BAI1 (inhibitor of BAX) and ABT-199 (inhibitor of BCL-2). Phenotypic and functional characteristics and cell survival were analysed by flow cytometry. CD8 T cells stimulated with high affinity peptide (N4) acquire effector phenotype (higher levels of CD25, CD69 and CD44) faster than cells stimulated with lower affinity peptide (Q4) which express higher levels of memory markers (CD127, CD62L and CCR7). Inhibition of the BAX molecule or incubation of cells with a BAI1 inhibitor had no effect on the formation of memory CD8 T cells, regardless of the affinity. Inhibition of the BCL-2 molecule (ABT-199 inhibitor) resulted in reduced survival of lower affinity cells (Q4) in the first days after stimulation at higher concentrations of inhibitors relative to higher affinity cells (N4 stimulated).
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:184:707942
Study programmeTitle: Study of Sanitary Engineering
Study programme type: university
Study level: graduate
Academic / professional title: magistar/magistra sanitarnog inženjerstva (magistar/magistra sanitarnog inženjerstva)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2021-06-23 07:52:58