Haematopoietic Stem Cell Transplantation Results in Extensive Remodelling of the Clonal T Cell Repertoire in Multiple Sclerosis

• DOI: 10.3389/fimmu.2022.798300
• Publication Date: 2022-02-07T05:50:33Z
• Authors: Jennifer Massey; Katherine Jackson; Mandeep Singh; Brendan Hughes; Barbara Withers; Carole Ford; Melissa Khoo; Kevin Hendrawan; John Zaunders; Bénédicte Charmet...; Rémi Cheynier; Fabio Luciani; David Ma; John Moore; Ian Sutton
• Keywords: CD4-Positive T-Lymphocytes; Multiple Sclerosis; Immunology; [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology; Hematopoietic Stem Cell Transplantation; T cell; RC581-607; CD8-Positive T-Lymphocytes; multiple sclerosis; Transplantation, Autologous; 3. Good health; TCR -T cell receptor; 03 medical and health sciences; 0302 clinical medicine; TCR - T cell receptor; aHSCT; Humans; Immunologic Factors; Lymphocyte Count; Immunologic diseases. Allergy; [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy; public clonotypes; Cells, Cultured

Autologous haematopoietic stem cell transplantation (AHSCT) is a vital therapeutic option for patients with highly active multiple sclerosis (MS). Rates of remission suggest AHSCT the most effective form immunotherapy in controlling disease. Despite an evolving understanding biology immune reconstitution following AHSCT, mechanism by which enables sustained disease beyond period lymphopenia remains to be elucidated. Auto-reactive T cells are considered central MS pathogenesis. Here, we analyse 36 months cohort patients. Through longitudinal analysis sorted naïve and memory clones, establish that induces profound changes dominant landscape both CD4+ CD8+ clones. Lymphopenia induced homeostatic proliferation followed clonal attrition; only 19% CD4 (p <0.025) 13% CD8 <0.005) clones from pre-transplant repertoire detected at months. Recovery thymically-derived occurs 12 ongoing months, however diversity populations not increased baseline suggesting principal durable after relates depletion putative auto-reactive In expressing risk allele HLA DRB1*15:01, public probed as potential biomarkers appears induce periods dynamic out post-transplant.