Figure 2 Proposed model of therapeutic mechanisms of AHSCT

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Figure 2 Proposed model of therapeutic mechanisms of AHSCT Figure 2 | Proposed model of therapeutic mechanisms of AHSCT. Ablative conditioning leads to radical depletion of pathogenic immune cells. During the 6 months after autologous haematopoietic stem cell transplantation (AHSCT), homeostatic expansion of the T cell repertoire produces CD8+ and, in smaller numbers, CD4+ T cells, and antigens are encountered through infection and reimmunization. These processes are associated with potentiation of immune regulation. Subsequently, and most effectively at 1–2 years after transplantation, immune renewal via thymopoiesis leads to increased numbers of naive CD4+ and CD8+ T cells and of CD31+ and signal joint T cell receptor excision circle positive (sjTREC+) recent thymic emigrants, which results in diversification of the T cell repertoire. In parallel, naive B cell reconstitution possibly restores the B cell repertoire and antibody diversity. Some normalization of gene expression profiles that favour restoration of tolerance has been demonstrated after completion of immune reconstitution at 2 years after AHSCT. Further work is required to demonstrate which immune changes are essential for the efficacy of AHSCT in suppressing the inflammatory disease activity in multiple sclerosis. MAIT, mucosal associated invariant T cell; NK, natural killer. Muraro, P. A. et al. (2017) Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis Nat. Rev. Neurol. doi:10.1038/nrneurol.2017.81