Natural killer cell phenotype and clinical response to interferon-beta therapy in multiple sclerosis

CD56bright NK cells, which may play a role in immunoregulation, are expanded in multiple sclerosis (MS) patients treated with immunomodulatory therapies such as daclizumab and interferon-beta (IFNβ). Yet, whether this NK cell subset is directly involved in the therapeutic effect is unknown. As NK receptor (NKR) expression by subsets of NK cells and CD8+ T lymphocytes is related to MS clinical course, we addressed whether CD56bright NK cells and NKR in IFNβ-treated MS patients differ according to the clinical response. IFNβ was associated to lower LILRB1+ and KIR + NK cells, and higher NKG2A + NK cell proportions, an immunophenotypic pattern mainly found in responders. After IFNβ treatment, a CD56bright NK cell expansion was significantly related to a positive clinical response. Our results reveal that IFNβ may promote in responders changes in the NK cell immunophenotype, corresponding to the profile found at early maturation stages of this lymphocyte lineage.

► We evaluated changes in NK cells in IFNβ-treated multiple sclerosis patients.
► Clinical response to IFNβ was related to an expansion of CD56bright NK cells.
► IFNβ decreases LILRB1 and KIRs, and increases NKG2A expression by NK cells.
► This immunophenotypic pattern was mainly found in responders to IFNβ.
► We conclude that IFNβ promotes in responders early maturation stages of NK cells.