京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20969号 / 医博第4315号 / 新制||医||1026(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 戸口田 淳也, 教授 濵﨑 洋子, 教授 三森 経世 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DGAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21342号 / 医博第4400号 / 新制||医||1031(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 長船 健二, 教授 羽賀 博典, 教授 妹尾 浩 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21627号 / 医博第4433号 / 新制||医||1033(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 平井 豊博, 教授 松原 和夫, 教授 羽賀 博典 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Memory T cells represent a specific subpopulation of cells formed during the first encounter with antigen. The main role of these cells is to elicit faster and more effective secondary response during reinfections. In transplant immunity, they may affect graft survival directly with donor-specific memory T cells or with cross-reactive virus-specific memory T cells. In this study, we focused on donor-specific and CMV-specific memory/effector T cells. We were interested in the effect of immunosuppressive therapy on the frequency of these cells in periphery. We found that the immunosuppression, prophylaxis and length of dialysis did not significantly affect the number of CMV-reactive cells 6 months after transplantation. We were also interested in the cross-reactivity between CMV and donor antigens, so-called heterologous immunity, which we verified by analyzing the TCR-β repertoire using next- generation sequencing (NGS) in CMV and donor-reactive T cells. Functional cross-reactive T cell clones (shared the same TCR-β sequence) were then found both in the peripheral blood of pre-transplant patients and in the post-transplant graft biopsy. We were also interested if long-term dialysis treatment affects immune memory. Dialysis therapy is often associated with the presence of poorly defined immune system...

No description available.

For over 50 years, bone marrow transplants have used CD34 to select stem cells. Recent research suggests that the most primitive hematopoietic stem cells (HSCs), long-term HSCs (LT-HSCs), are found in the CD34-negative portion of murine and human bone marrow cells. LT-HSCs are rare and cannot be isolated directly, making them difficult to study. During a bone marrow transplant, these stem cells must find their way to the bone marrow niche and engraft to become blood cells. Several cell adhesion molecules on the stem cell engage with their ligands on the endothelial cells lining the bone marrow vasculature to control this migration. Human LT-HSCs cells do not migrate and engraft well when infused in vivo, which may be due to a lack of adhesion molecules. Thus, the goal of this study was to determine whether this population of HSCs lacked adhesion systems (proteins and carbohydrate modifications) and, if so, to improve their migration and engraft ability by modifying key mechanistic steps in the adhesion cascade. Therefore, we investigated how distinct hematopoietic stem cell populations migrate to the bone marrow using adhesion mechanisms. This study represents the first direct analysis of adhesion molecules expression in LT-HSC and will potentially shed light on methods to optimally use these very valuable cells in the clinical bone marrow and cord blood transplants worldwide.

No description available.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24530号 / 医博第4972号 / 新制||医||1065(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 小濱 和貴, 教授 小林 恭, 教授 川口 義弥 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Rapidly progressive diffuse systemic sclerosis (dSSc) is a life-threatening condition characterized by increased mortality with few effective therapies, typically only helpful in stabilizing disease. Autologous hematopoietic stem cell transplantation (AHSCT) is the only treatment that has demonstrated improved survival. Despite promising results from three randomized controlled trials (RCTs), best practice use of AHSCT in the real-world setting is not well established. The primary objective of this thesis was to summarize the clinical efficacy, limitations and utilization of AHSCT in the management of rapidly progressive dSSc. Specifically, we conducted (1) a systematic review to describe the efficacy of AHSCT in dSSc as well as practice variation in patient selection and treatment regimens; and (2) a multicenter retrospective cohort study to compare outcomes for subjects who received AHSCT in France compared to those who received conventional care in Canada. There was important variability in the criteria for patient selection and treatment protocols. While AHSCT is associated with improved overall survival, skin fibrosis and lung function, further studies are needed to understand its potential for expanded eligibility and effects on other disease manifestations.

No description available.