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

Front Immunol. 2018 Apr 20:9:767. doi: 10.3389/fimmu.2018.00767. eCollection 2018.

Abstract

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.

Keywords: T cell receptor repertoire; T cell reconstitution; autoimmune disease; autologous hematopoietic stem cell transplantation; regulatory T cell.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / therapy*
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • T-Lymphocytes / immunology*
  • Transplantation, Autologous