title: T cell repertoire following autologous stem cell transplantation for multiple sclerosis.
abstract: Autologous hematopoietic stem cell transplantation (HSCT) is commonly employed for hematologic and non-hematologic malignancies. In clinical trials, HSCT has been evaluated for severe autoimmunity as a method to "reset" the immune system and produce a new, non-autoimmune repertoire. While the feasibility of eliminating the vast majority of mature T cells is well established, accurate and quantitative determination of the relationship of regenerated T cells to the baseline repertoire has been difficult to assess. Here, in a phase II study of HSCT for poor-prognosis multiple sclerosis, we used high-throughput deep TCRβ chain sequencing to assess millions of individual TCRs per patient sample. We found that HSCT has distinctive effects on CD4+ and CD8+ T cell repertoires. In CD4+ T cells, dominant TCR clones present before treatment were undetectable following reconstitution, and patients largely developed a new repertoire. In contrast, dominant CD8+ clones were not effectively removed, and the reconstituted CD8+ T cell repertoire was created by clonal expansion of cells present before treatment. Importantly, patients who failed to respond to treatment had less diversity in their T cell repertoire early during the reconstitution process. These results demonstrate that TCR characterization during immunomodulatory treatment is both feasible and informative, and may enable monitoring of pathogenic or protective T cell clones following HSCT and cellular therapies.
authors: Paolo A
authors: PA
authors: Muraro
authors: Harlan
authors: H
authors: Robins
authors: Sachin
authors: S
authors: Malhotra
authors: Michael
authors: M
authors: Howell
authors: Deborah
authors: D
authors: Phippard
authors: Cindy
authors: C
authors: Desmarais
authors: Alessandra
authors: A
authors: de Paula Alves Sousa
authors: Linda M
authors: LM
authors: Griffith
authors: Noha
authors: N
authors: Lim
authors: Richard A
authors: RA
authors: Nash
authors: Laurence A
authors: LA
authors: Turka
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D017322:Clinical Trials, Phase II as Topic; D018380:Hematopoietic Stem Cell Transplantation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007165:Immunosuppression Therapy; D015337:Multicenter Studies as Topic; D009103:Multiple Sclerosis / Q000276:immunology / Q000628:therapy*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta