T-cell responses after haematopoietic stem cell transplantation for aggressive relapsing-remitting multiple sclerosis

Immunology. 2013 Oct;140(2):211-9. doi: 10.1111/imm.12129.


Autologous haematopoietic stem cell transplantation (HSCT) for relapsing-remitting multiple sclerosis is a potentially curative treatment, which can give rise to long-term disease remission. However, the mode of action is not yet fully understood. The aim of the study was to evaluate similarities and differences of the CD4(+) T-cell populations between HSCT-treated patients (n = 12) and healthy controls (n = 9). Phenotyping of memory T cells, regulatory T (Treg) cells and T helper type 1 (Th1) and type 17 (Th17) cells was performed. Further, T-cell reactivity to a tentative antigen, myelin oligodendrocyte glycoprotein, was investigated in these patient populations. Patients treated with natalizumab (n = 15) were included as a comparative group. White blood cells were analysed with flow cytometry and T-cell culture supernatants were analysed with magnetic bead panel immunoassays. HSCT-treated patients had similar levels of Treg cells and of Th1 and Th17 cells as healthy subjects, whereas natalizumab-treated patients had lower frequencies of Treg cells, and higher frequencies of Th1 and Th17 cells. Cells from HSCT-treated patients cultured with overlapping peptides from myelin oligodendrocyte glycoprotein produced more transforming growth factor-β1 than natalizumab-treated patients, which suggests a suppressive response. Conversely, T cells from natalizumab-treated patients cultured with those peptides produced more interleukin-17 (IL-17), IL-1 and IL-10, indicating a Th17 response. In conclusion, we demonstrate circumstantial evidence for the removal of autoreactive T-cell clones as well as development of tolerance after HSCT. These results parallel the long-term disease remission seen after HSCT.

Trial registration: ClinicalTrials.gov NCT00273364.

Keywords: haematopoietic stem cell transplantation; multiple sclerosis; natalizumab; neuroimmunology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Separation
  • Female
  • Flow Cytometry
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy
  • Multiple Sclerosis, Relapsing-Remitting / immunology*
  • Multiple Sclerosis, Relapsing-Remitting / surgery*
  • Natalizumab
  • Young Adult


  • Antibodies, Monoclonal, Humanized
  • Natalizumab

Associated data

  • ClinicalTrials.gov/NCT00273364