T cell repertoire following autologous stem cell transplantation for multiple sclerosis


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Autologous haematopoietic stem cell transplantation (HSCT) is typically used in haematologic and non-haematologic malignancies. In clinical trials, HSCT has also 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 (MS), the researchers used high-throughput deep TCR-beta chain sequencing to assess millions of individual TCRs per individual patient sample. This was done before and at two time points after autologous HSCT in a cohort of 24 patients. The study showed 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. Demonstrating that TCR characterization during immunomodulatory treatment may enable monitoring of T cell clones following HSCT and cellular therapies.

Muraro, P. et al. 2014. T cell repertoire following autologous stem cell transplantation for multiple sclerosis. The Journal of Clinical Investigation.

 
 
 
 
 
 
International Union of Immunological SocietiesUniversity of South AfricaInstitute of Infectious Disease and Molecular MedicineScience Education PrizesElizabeth Glazer Pediatric Aids FoundationAlere