{"id":{"repo_id":"unsw","oai_identifier":"oai:unsworks.library.unsw.edu.au:1959.4/70972"},"canonical_url":"https://search.dev.ndltd.org/etd/unsw/oai:unsworks.library.unsw.edu.au:1959.4/70972","repository":{"repo_id":"unsw","name":"University of New South Wales","base_url":"https://unsworks.unsw.edu.au/oai/provider"},"display":{"title":"Immunotolerance regeneration by T regulatory cells in autologous haematopoietic stem cell transplantation for multiple sclerosis","abstract":"The breakdown of immunological self-tolerance manifests clinically as autoimmune diseases, such as Multiple sclerosis (MS), an autoimmune disease of the central nervous system (CNS). Autologous haematopoietic stem cell transplantation (AHSCT) has received increasing attention in recent years as a therapeutic option for treatment refractory MS. AHSCT has been proposed to induce long-term remission by initiating an immune system “reboot” via the chemotherapy-driven ablation of autoreactive immune cells and the regeneration of immunoregulatory lymphocytes, such as CD4+ T regulatory cells (Tregs). Tregs expressing the ectonucleotidase enzyme CD39 exert immunoregulatory function by suppressing T helper (Th)17-related immune responses, which has been significantly associated with MS pathogenesis. However, this immunoregulatory function was reported to be decreased in MS patients. CD39 expression, and its corresponding immunological function, on Tregs is determined by the genetic polymorphism of the CD39 gene (at position rs_10748643), where its expression may be low (AA-genotype), medium (AG-genotype) or high (GG-genotype). Hence, CD39 genetic polymorphism may significantly determine CD39+ Treg function and reconstitution in MS patients and/or influence the immunological shift in patients following AHSCT. Three novel aspects regarding Treg-associated tolerance regeneration in MS patients following AHSCT are presented in this thesis: 1) although there is no direct clinical correlation, this is the first study investigating the role of CD39 genetic polymorphism in immune reconstitution, cytokine evolution, and Treg function following AHSCT in MS patients (Chapters 3, 4, and 6); 2) significant and long-term reductions in Th17- and Th1-related cytokines post-AHSCT further support the ongoing hypothesis that AHSCT induces an anti-inflammatory shift in MS patients (Chapter 4), and 3) to the best of this author’s knowledge, this thesis was the first to report that MS patients without clinical relapse post-AHSCT exhibit significant improvements in CD4+ Treg suppressive function at 24 months post-AHSCT (Chapter 6) and consistent suppression of Th17 cytokines at all timepoints up to 24 months post-AHSCT (Chapter 4). Future studies must address the exact immunoregulatory pathway that is regenerated in Tregs following AHSCT in MS patients.","abstract_html":"The breakdown of immunological self-tolerance manifests clinically as autoimmune diseases, such as Multiple sclerosis (MS), an autoimmune disease of the central nervous system (CNS). Autologous haematopoietic stem cell transplantation (AHSCT) has received increasing attention in recent years as a therapeutic option for treatment refractory MS. AHSCT has been proposed to induce long-term remission by initiating an immune system “reboot” via the chemotherapy-driven ablation of autoreactive immune cells and the regeneration of immunoregulatory lymphocytes, such as CD4+ T regulatory cells (Tregs). Tregs expressing the ectonucleotidase enzyme CD39 exert immunoregulatory function by suppressing T helper (Th)17-related immune responses, which has been significantly associated with MS pathogenesis. However, this immunoregulatory function was reported to be decreased in MS patients. CD39 expression, and its corresponding immunological function, on Tregs is determined by the genetic polymorphism of the CD39 gene (at position rs_10748643), where its expression may be low (AA-genotype), medium (AG-genotype) or high (GG-genotype). Hence, CD39 genetic polymorphism may significantly determine CD39+ Treg function and reconstitution in MS patients and/or influence the immunological shift in patients following AHSCT. Three novel aspects regarding Treg-associated tolerance regeneration in MS patients following AHSCT are presented in this thesis: 1) although there is no direct clinical correlation, this is the first study investigating the role of CD39 genetic polymorphism in immune reconstitution, cytokine evolution, and Treg function following AHSCT in MS patients (Chapters 3, 4, and 6); 2) significant and long-term reductions in Th17- and Th1-related cytokines post-AHSCT further support the ongoing hypothesis that AHSCT induces an anti-inflammatory shift in MS patients (Chapter 4), and 3) to the best of this author’s knowledge, this thesis was the first to report that MS patients without clinical relapse post-AHSCT exhibit significant improvements in CD4+ Treg suppressive function at 24 months post-AHSCT (Chapter 6) and consistent suppression of Th17 cytokines at all timepoints up to 24 months post-AHSCT (Chapter 4). Future studies must address the exact immunoregulatory pathway that is regenerated in Tregs following AHSCT in MS patients.","abstract_has_math":false,"creators":["Hendrawan, Kevin"],"institution":"UNSW, Sydney","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2021,"date_issued":"2021","date_published":"2021","updated_at":"2026-07-24T05:32:14Z","subjects":["MS","Tregs","AHSCT"],"languages":["EN"],"rights":["open access","CC BY-NC-ND 3.0","free_to_read"],"rights_urls":["https://purl.org/coar/access_right/c_abf2","https://creativecommons.org/licenses/by-nc-nd/3.0/au/"],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["https://doi.org/10.26190/unsworks/2309"],"render_values":[{"text":"https://doi.org/10.26190/unsworks/2309","href":"https://doi.org/10.26190/unsworks/2309","code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/1959.4/70972","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Hendrawan, Kevin"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2021"]},{"key":"dc:publisher","label":"Institution","values":["UNSW, Sydney"]},{"key":"dc:type","label":"Dc Type","values":["doctoral thesis","http://purl.org/coar/resource_type/c_db06"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["MS","Tregs","AHSCT"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["EN"]},{"key":"dc:rights","label":"Dc Rights","values":["open access","https://purl.org/coar/access_right/c_abf2","CC BY-NC-ND 3.0","https://creativecommons.org/licenses/by-nc-nd/3.0/au/","free_to_read"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/1959.4/70972","https://unsworks.unsw.edu.au/bitstreams/4dcb889a-37a5-4b4a-b99b-4b8bd1f4586c/download","https://doi.org/10.26190/unsworks/2309"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The breakdown of immunological self-tolerance manifests clinically as autoimmune diseases, such as Multiple sclerosis (MS), an autoimmune disease of the central nervous system (CNS). Autologous haematopoietic stem cell transplantation (AHSCT) has received increasing attention in recent years as a therapeutic option for treatment refractory MS. AHSCT has been proposed to induce long-term remission by initiating an immune system “reboot” via the chemotherapy-driven ablation of autoreactive immune cells and the regeneration of immunoregulatory lymphocytes, such as CD4+ T regulatory cells (Tregs). Tregs expressing the ectonucleotidase enzyme CD39 exert immunoregulatory function by suppressing T helper (Th)17-related immune responses, which has been significantly associated with MS pathogenesis. However, this immunoregulatory function was reported to be decreased in MS patients. CD39 expression, and its corresponding immunological function, on Tregs is determined by the genetic polymorphism of the CD39 gene (at position rs_10748643), where its expression may be low (AA-genotype), medium (AG-genotype) or high (GG-genotype). Hence, CD39 genetic polymorphism may significantly determine CD39+ Treg function and reconstitution in MS patients and/or influence the immunological shift in patients following AHSCT. Three novel aspects regarding Treg-associated tolerance regeneration in MS patients following AHSCT are presented in this thesis: 1) although there is no direct clinical correlation, this is the first study investigating the role of CD39 genetic polymorphism in immune reconstitution, cytokine evolution, and Treg function following AHSCT in MS patients (Chapters 3, 4, and 6); 2) significant and long-term reductions in Th17- and Th1-related cytokines post-AHSCT further support the ongoing hypothesis that AHSCT induces an anti-inflammatory shift in MS patients (Chapter 4), and 3) to the best of this author’s knowledge, this thesis was the first to report that MS patients without clinical relapse post-AHSCT exhibit significant improvements in CD4+ Treg suppressive function at 24 months post-AHSCT (Chapter 6) and consistent suppression of Th17 cytokines at all timepoints up to 24 months post-AHSCT (Chapter 4). Future studies must address the exact immunoregulatory pathway that is regenerated in Tregs following AHSCT in MS patients."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Immunotolerance regeneration by T regulatory cells in autologous haematopoietic stem cell transplantation for multiple sclerosis"]}]}],"canonical_facts":{"dc:creator":["Hendrawan, Kevin"],"dc:date":["2021"],"dc:description":["The breakdown of immunological self-tolerance manifests clinically as autoimmune diseases, such as Multiple sclerosis (MS), an autoimmune disease of the central nervous system (CNS). Autologous haematopoietic stem cell transplantation (AHSCT) has received increasing attention in recent years as a therapeutic option for treatment refractory MS. AHSCT has been proposed to induce long-term remission by initiating an immune system “reboot” via the chemotherapy-driven ablation of autoreactive immune cells and the regeneration of immunoregulatory lymphocytes, such as CD4+ T regulatory cells (Tregs). Tregs expressing the ectonucleotidase enzyme CD39 exert immunoregulatory function by suppressing T helper (Th)17-related immune responses, which has been significantly associated with MS pathogenesis. However, this immunoregulatory function was reported to be decreased in MS patients. CD39 expression, and its corresponding immunological function, on Tregs is determined by the genetic polymorphism of the CD39 gene (at position rs_10748643), where its expression may be low (AA-genotype), medium (AG-genotype) or high (GG-genotype). Hence, CD39 genetic polymorphism may significantly determine CD39+ Treg function and reconstitution in MS patients and/or influence the immunological shift in patients following AHSCT. Three novel aspects regarding Treg-associated tolerance regeneration in MS patients following AHSCT are presented in this thesis: 1) although there is no direct clinical correlation, this is the first study investigating the role of CD39 genetic polymorphism in immune reconstitution, cytokine evolution, and Treg function following AHSCT in MS patients (Chapters 3, 4, and 6); 2) significant and long-term reductions in Th17- and Th1-related cytokines post-AHSCT further support the ongoing hypothesis that AHSCT induces an anti-inflammatory shift in MS patients (Chapter 4), and 3) to the best of this author’s knowledge, this thesis was the first to report that MS patients without clinical relapse post-AHSCT exhibit significant improvements in CD4+ Treg suppressive function at 24 months post-AHSCT (Chapter 6) and consistent suppression of Th17 cytokines at all timepoints up to 24 months post-AHSCT (Chapter 4). Future studies must address the exact immunoregulatory pathway that is regenerated in Tregs following AHSCT in MS patients."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/1959.4/70972","https://unsworks.unsw.edu.au/bitstreams/4dcb889a-37a5-4b4a-b99b-4b8bd1f4586c/download","https://doi.org/10.26190/unsworks/2309"],"dc:language":["EN"],"dc:publisher":["UNSW, Sydney"],"dc:rights":["open access","https://purl.org/coar/access_right/c_abf2","CC BY-NC-ND 3.0","https://creativecommons.org/licenses/by-nc-nd/3.0/au/","free_to_read"],"dc:subject":["MS","Tregs","AHSCT"],"dc:title":["Immunotolerance regeneration by T regulatory cells in autologous haematopoietic stem cell transplantation for multiple sclerosis"],"dc:type":["doctoral thesis","http://purl.org/coar/resource_type/c_db06"]},"updated_at":"2026-07-24T05:32:14Z"}