Journal
FRONTIERS IN IMMUNOLOGY
Volume 9, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2018.00767
Keywords
autologous hematopoietic stem cell transplantation; autoimmune disease; T cell reconstitution; T cell receptor repertoire; regulatory T cell
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Funding
- VIDI from The Netherlands Organization for Health Research and Development (ZonMw) [91714332]
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Autologous hematopoietic stem cell transplantation (aHSCT) for autoimmune diseases has been applied for two decades as a treatment for refractory patients with progressive disease. The rationale behind aHSCT is that high-dose immunosuppression eliminates autoreactive T and B cells, thereby resetting the immune system. Post-aHSCT the cytotoxic CD8(+) T cells normalize via clonal expansion due to homeostatic proliferation within a few months. CD4(+) T cells recover primarily via thymopoiesis resulting in complete renewal of the T cell receptor (TCR) repertoire which requires years or never normalize completely. The increase in naive T cells inducing immune tolerance, renewal of especially the regulatory TCR repertoire, and a less pro-inflammatory functional profile of the CD4(+) T cells seem essential for successful immune reconstitution inducing long-term remission. There is currently a knowledge gap regarding the immune response in tissue sites post-aHSCT, as well as disease-specific factors that may determine remission or relapse. Future studies on lymphocyte dynamics and function may pave the way for optimized conditioning regimens with a more individualized approach.
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