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CD8 T Cell Differentiation During Immune Responses Sara Sofia De Campos Pereira Lemos

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CD8 T cell differentiation during immune responses Sara Sofia de Campos Pereira Lemos To cite this version: Sara Sofia de Campos Pereira Lemos. CD8 T cell differentiation during immune responses. Immunol- ogy. Université René Descartes - Paris V, 2014. English. NNT : 2014PA05T009. tel-01059806 HAL Id: tel-01059806 https://tel.archives-ouvertes.fr/tel-01059806 Submitted on 2 Sep 2014 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. UNIVERSITÉ PARIS DESCARTES FACULTÉ DE MEDECINE-site Necker INSERM U1020 (ex U591) _______________________________________________________________________ THÈSE Pour obtenir le grade de DOCTEUR Sciences de la Vie et de la Santé Discipline: Immunologie École Doctoral: Gc2iD Présentée et soutenue publiquement par Sara Sofia de Campos Pereira Lemos Le 23 Mai 2014 CD8 T cell differentiation during immune responses Jury: Dr. Jacqueline MARVEL Rapporteur Dr. Sylvie GUERDER Rapporteur Dr. Jérôme DELON Examinateur Dr. Nicolas BLANCHARD Examinateur Dr. Benedita ROCHA Directeur de these 1 To a wonderful person, an extraordinary woman and an amazing mother... my mother, Arlete Pereira “The first precept was never to accept a thing as true until I knew it as such without a single doubt.” René Descartes (French philosopher and scientist) “We live where no one knows the answer and the struggle is to figure out the question” Joshua Schimel (in “Writing Science” book). “ To be great, be whole; Exclude nothing, exaggerate nothing that is not you. Be whole in everything. Put all you are Into the smallest thing you do. So, in each lake, the moon shines with splendor Because it blooms up above.” Fernando Pessoa (Portuguese poet) “The beauty of life is not about finding something big enough, but rather on finding something deep enough! Sara Lemos (a dreamer!) 2 Acknowledgments My very first and respectful acknowledgment I owe to an extraordinary scientist and remarkable person: my supervisor Benedita ROCHA. Thank you for accepting me in your lab, for supervising this work, for all the opportunities given to grow as a PhD student and as a person, for all the freedom at the bench, and yet for always pushing me forward. It was such an HONOR and CHALLENGE to work with you! To all jury members, a special thank you for accepting to evaluate this thesis work. To Jacqueline MARVEL and Sylvie GUERDER a particularly thank you for your precise and critical analyze of my thesis work as rapporteurs. To Jérôme DELON and Nicolas BLANCHARD a special thank you for your patience in waiting for the final version and for revising this work as examinateurs. It was also an HONOR to have all of you judging this work. From Institut Pasteur, I would like to thank Antonio FREITAS for providing us with OT-1 mice, Matthew ALBERT for MyD88-/- mice and Hélène DECALUWE for preparing LCMV and performing the corresponding immunizations. From Necker Institute, I would like to thank Alain CHARBIT at INSERM U1002 for his advice and bacteria expertise, and for using his bacteria lab facilities too. To his team members, thank you for always making me feel truly welcome in a “bacterial” lab (my 2nd lab/home!). Thank you to all members of INSERM U1020 (ex U591). Sophie EZINE for all the B6 Thy1.1 mice given, for pushing my organizational skill to top levels and for always being there to solve lab problems and to guide me in the thesis manuscript/defense procedures. Orly AZOGUI for truly understanding my complainings about FlowJo crashes and for always being available to discuss science! (a special thanks for precious help with my thesis summary in French too). Florence VASSEUR and Pierric PARENT for big help with mice during the lab moving from Necker Institut to Broussais Hospital. Agnes LEGRAND for precious help on single-cell multiplex RT-PCR experiments, for teaching me SDS program, for all your sincerity, efficiency and friendship. To all secretaries, for patience with my complicated orders of new products or mice. Chantal for helping me with DNA extractions for mice genotyping (a tremendous time consuming job to do alone!). Benoir for efficiently providing material disappeared at the last minute. Evelyn, for always reminding me that the world is round and that sometimes we need to say a big NO (I should practice it more!!!). To the new members of the new INSERM U1151-team 13, Flora ZAVALA and Sarantis KORNIOTIS, a big thank you for your kindness, happy “bonjours” and powerful “courage Sara, c’est bientôt la fin!”, during the last tough weeks of thesis writing! To Cesar EVARISTO and Patricia SANTOS for being awesome "lab parents" to me and Miguel, for NEVER having denied a scientific discussion, for your truth friendship and for all the tuga's dinners around Paris! To Cesar, extra thanks for being ALWAYS available to teach me: at 4 am when dilacerating spleens to plate; at 2 am when fighting for a 3rd (not broken) Canto to not lose our incredible amount of work; and even at 7.000 Km away, for answering all my specific questions, or sending me your data to combine with mine (what a nightmare!). My gratefulness and respect to you are infinite! Thanks for the astonishing book “Writing Science”. To Patricia extra thanks for your objectivity, sincerity and CLEVER talks either about science or life! I particularly enjoyed the ones in the corridors or those seated on FACS flow boxes! To Miguel FERREIRA, a true "brother in science", thank you for the immense patience to discuss with me homologous recombination tricks (as well as a bunch of other scientific stuff) and for being always on 3 my right side (of the office) to listen, to talk, to share, or simply just to be there with a true friendship. An extra thanks for being the only one TRULY understanding the meaning of a back pain, or a cold feeling when huge experiments take more than 20h. (Contributions to my French metro-poetry posters’ collection, not forgotten!). To Vanessa ZEPPONI, my "French lab sister", an immense thank you for always being there, at my left side (of the bench), for teaching me new concepts and views about life, and for ALL FUNNY moments lived in the lab and around Paris! An extra thank you for beers or Japanese moments of friendship (Disneyland and a lot of not taken T3 tramways moments too!) and also for always helping me with French language, essential to survive in the lab and in the Paris-quotidian life! To Hsueh SUNG, a big thank you for being always available to answer, at distance, my 1001 questions about practical details of the CD8 inflammatory project. Thanks a lot for all the true friendship, PATIENCE AND RESPECT (it was a pity that we couldn´t work together on the bench!). To all current postdocs, an enormous thank you for the “mental support” during my thesis writing (advice, tricks and frustrations included! you know how hard it was to leave my lovely bench!). Alessia GALGANO for all the discussions about molecular biology and lab (dis)organization. Marie CHERRIER, for sharing with me much more than the office in this last year, for all your sincerity, advice, friendship, scientific talks, and good lab mood (once one is an OUTSTANDING person, one will be an outstanding group leader too. All the best!). To Gerald KRENN and Alexander BARINOV… to you “my” guys… My gratitude and respect are INFINITE. A truthful thank you for all your friendship, your sincerity, wise advice, men’s objectivity, confidence and beers that always comforted me! I’ll miss a lot our Austro-Russian-Luso “canteen-gang”!!! A special thanks for the multicultural "soirées" in the company of your wives too. To Ricarda KRENN, a special thanks for reviewing my English writing. To Pedro GONÇALVES for friendship and all the supporting: Write Sara!!! Write Sara!!! I’m still deeply grateful to Gerald, Alexander, Pedro and Vanessa for helping me when my computer broke down 3 days before sending my manuscript to evaluation! (what a panic attack!). To the current students Victoria M. LOPEZ and Thomas HARBONNIER, thank you for all the good moments, friendship, and “student’s solidarity”! (good luck!!!). To former members of the Necker lab with whom I also shared big moments around pipettes, reagents and laughs, a sincere thank you for being so nice with me: Sylvain MEUNIER, Laetitia PEAUDECERF, Lamina SKHIRI, Marie BÉDORA, Amine BOUDIL, and Kateryna KOZYRYTSKA. Special thanks to all the" petits" that were quite big friends: Paula MARTINS, Cédric DONATHELLO and Coraline CANIVET for the "on mange the hors!", Yann BECKER for "poker face" laughing moments and Laurent BEZIAUD for COMEDY moments and for being so present and supportive (and I am so sorry for being always late! - I’m a disaster in terms of orientation !!!) (good luck for your thesis writing!). An IMMEASURABLE thank you to my (maternal) FAMILY! My MOTHER, for unconditional love and support during every single day of my life! My UNCLES, those who welcomed me several times at the airport, or those who always made my favorite chocolate cake for departure! My COUSINS, those who always say to me “Sara wake up! You live like a nomad!”, those who never deny card games during our gatherings of family dinners, and yet, the ones who never let me sing alone (in particular Linkin Park songs!) and always gave me those sincere and powerful hugs! My maternal GRANDPARENTS and GREAT-UNCLES for always being there with open loving arms.
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    Supplementary Table 6. Processes associated to the 2037 SCL candidate target genes ID Symbol Entrez Gene Name Process NM_178114 AMIGO2 adhesion molecule with Ig-like domain 2 adhesion NM_033474 ARVCF armadillo repeat gene deletes in velocardiofacial syndrome adhesion NM_027060 BTBD9 BTB (POZ) domain containing 9 adhesion NM_001039149 CD226 CD226 molecule adhesion NM_010581 CD47 CD47 molecule adhesion NM_023370 CDH23 cadherin-like 23 adhesion NM_207298 CERCAM cerebral endothelial cell adhesion molecule adhesion NM_021719 CLDN15 claudin 15 adhesion NM_009902 CLDN3 claudin 3 adhesion NM_008779 CNTN3 contactin 3 (plasmacytoma associated) adhesion NM_015734 COL5A1 collagen, type V, alpha 1 adhesion NM_007803 CTTN cortactin adhesion NM_009142 CX3CL1 chemokine (C-X3-C motif) ligand 1 adhesion NM_031174 DSCAM Down syndrome cell adhesion molecule adhesion NM_145158 EMILIN2 elastin microfibril interfacer 2 adhesion NM_001081286 FAT1 FAT tumor suppressor homolog 1 (Drosophila) adhesion NM_001080814 FAT3 FAT tumor suppressor homolog 3 (Drosophila) adhesion NM_153795 FERMT3 fermitin family homolog 3 (Drosophila) adhesion NM_010494 ICAM2 intercellular adhesion molecule 2 adhesion NM_023892 ICAM4 (includes EG:3386) intercellular adhesion molecule 4 (Landsteiner-Wiener blood group)adhesion NM_001001979 MEGF10 multiple EGF-like-domains 10 adhesion NM_172522 MEGF11 multiple EGF-like-domains 11 adhesion NM_010739 MUC13 mucin 13, cell surface associated adhesion NM_013610 NINJ1 ninjurin 1 adhesion NM_016718 NINJ2 ninjurin 2 adhesion NM_172932 NLGN3 neuroligin
  • Late Stages of T Cell Maturation in the Thymus

    Late Stages of T Cell Maturation in the Thymus

    ARTICLES Late stages of T cell maturation in the thymus involve NF-B and tonic type I interferon signaling Yan Xing, Xiaodan Wang, Stephen C Jameson & Kristin A Hogquist Positive selection occurs in the thymic cortex, but critical maturation events occur later in the medulla. Here we defined the precise stage at which T cells acquired competence to proliferate and emigrate. Transcriptome analysis of late gene changes suggested roles for the transcription factor NF-B and interferon signaling. Mice lacking the inhibitor of NF-B (IB) kinase (IKK) kinase TAK1 underwent normal positive selection but exhibited a specific block in functional maturation. NF-B signaling provided protection from death mediated by the cytokine TNF and was required for proliferation and emigration. The interferon signature was independent of NF-B; however, thymocytes deficient in the interferon- (IFN-) receptor IFN-R showed reduced expression of the transcription factor STAT1 and phenotypic abnormality but were able to proliferate. Thus, both NF-B and tonic interferon signals are involved in the final maturation of thymocytes into naive T cells. T cell development occurs in the thymus, which provides a unique reside predominantly in the medulla; however, not all SP thymocytes microenvironment and presents ligands consisting of self peptide and are equivalent. major histocompatibility complex (MHC) molecules to T cell anti- CD24hiQa2lo SP thymocytes have been defined as ‘semi-mature’ gen receptors (TCRs). In the cortex of the thymus, low-affinity TCR and have been shown to be susceptible to apoptosis when triggered interactions initiate positive selection signals in CD4+CD8+ double- through the TCR6.