A CD8+ NK cell transcriptomic signature associated with clinical outcome in relapsing remitting multiple sclerosis

Nat Commun. 2021 Jan 27;12(1):635. doi: 10.1038/s41467-020-20594-2.


Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) with the majority of cases characterised by relapsing/remitting (RRMS) attacks of neurologic dysfunction followed by variable resolution. Improving clinical outcomes in RRMS requires both a better understanding of the immunological mechanisms driving recurrent demyelination and better means of predicting future disease course to facilitate early targeted therapy. Here, we apply hypothesis-generating network transcriptomics to CD8+ cells isolated from patients in RRMS, identifying a signature reflecting expansion of a subset of CD8+ natural killer cells (NK8+) associated with favourable outcome. NK8+ are capable of regulating CD4+ T cell activation and proliferation in vitro, with reduced expression of HLA-G binding inhibitory receptors and consequent reduced sensitivity to HLA-G-mediated suppression. We identify surrogate markers of the NK8+ signature in peripheral blood leucocytes and validate their association with clinical outcome in an independent cohort, suggesting their measurement may facilitate early, targeted therapy in RRMS.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / ultrastructure
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • HLA-G Antigens / metabolism
  • Humans
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / ultrastructure
  • Lymphocyte Activation / genetics
  • Multiple Sclerosis, Relapsing-Remitting / genetics*
  • Multiple Sclerosis, Relapsing-Remitting / immunology*
  • Reproducibility of Results
  • Risk Factors
  • Transcriptome / genetics*
  • Treatment Outcome


  • HLA-G Antigens