Immune responses to polyclonal T-cell vaccination in patients with progressive multiple sclerosis

J Immunotoxicol. 2016 Nov;13(6):879-884. doi: 10.1080/1547691X.2016.1223767. Epub 2016 Sep 7.

Abstract

The overall objective of disease management in autoimmune diseases is to suppress chronic inflammation and prevent organ damage. Therapies often revolve around five drug classes: non-steroidal anti-inflammatory drugs (NSAIDS), anti-malarials, steroids, immunosuppressants, and bio-therapies. However, none of these is a 'cure' and each displays a potential for adverse events. In particular, while all of them suppress harmful autoimmune responses, they also impact on useful protective immune responses. T-Cell receptor (TCR) immunogenicity provides a rationale for T-cell vaccinations to induce anti-idiotypic immune responses with the purpose of down-regulating functionality of idiotype-bearing self-reactive T-cells. To explore this, in this study, 39 patients with progressive (chronic) multiple sclerosis (MS) were multiply immunized with autological polyclonal T-cell vaccines (TCVs). None of the TCV-treated patients experienced any significant side-effects during the entire follow-up period (2 years). T-Cell vaccination had no significant effects on T-cell sub-population contents in the blood of MS patients after 2 years of immunotherapy initiation. However, a substantial reduction in the frequency of CD4+ and CD8+ memory T-cells able to produce interferon (IFN)-γ following activation were noted in the blood of TCV-treated patients. Moreover, significant and sustained reduction in plasma IFNγ levels and concomitant increases in interleukin (IL)-4 levels were documented in these samples. The TCV-treated subjects, however, exhibited no significant changes in plasma IL-17 and IL-18. More importantly was a significant decline in proliferative T-cell responses to myelin antigens in the TCV-treated patients, indicating attenuation of myelin-specific T-cell activity. Collectively, the results suggest that polyclonal T-cell vaccination is safe to use, able to induce measurable, long-lasting, anti-inflammatory immune effects in patients with advanced MS.

Keywords: Progressive multiple sclerosis; immune response; memory T-cell; polyclonal T-cell vaccine; regulatory T-cell.

MeSH terms

  • Adult
  • Antibodies, Anti-Idiotypic / immunology
  • Antibodies, Anti-Idiotypic / metabolism*
  • Cells, Cultured
  • Cytokines / metabolism
  • Female
  • Follow-Up Studies
  • Humans
  • Immunity
  • Immunologic Memory
  • Immunosuppression
  • Immunotherapy, Adoptive / methods*
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Multiple Sclerosis, Chronic Progressive / immunology*
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / transplantation
  • Vaccination
  • Vaccines / immunology*
  • Young Adult

Substances

  • Antibodies, Anti-Idiotypic
  • Cytokines
  • Receptors, Antigen, T-Cell
  • Vaccines