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Resetting the T Cell Compartment in Autoimmune Diseases With Autologous Hematopoietic Stem Cell Transplantation: An Update

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...

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Detalles Bibliográficos
Autores principales: Lutter, Lisanne, Spierings, Julia, van Rhijn-Brouwer, Femke C. C., van Laar, Jacob M., van Wijk, Femke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5920130/
https://www.ncbi.nlm.nih.gov/pubmed/29731752
http://dx.doi.org/10.3389/fimmu.2018.00767
Descripción
Sumario: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 naïve 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.