Immunologic and MRI markers of the therapeutic effect of IFN-β-1a in relapsing-remitting MS

Associations between baseline immunologic markers and lesion volume in the subgroup of patients with active disease (≥1 relapse in the year before baseline). (A) Baseline percentage of CD8⁺ T cells expressing intracellular IL-22 correlated positively with baseline T2 lesion volume. (B) Baseline percentages of CD8⁺ cells expressing intracellular IL-17A correlated positively with baseline T2 lesion volume. (C) Baseline percentages of CD8⁺ cells expressing intracellular IL-17A correlated positively with baseline T1 lesion volume. Fresh peripheral blood mononuclear cells were stimulated with PMA and ionomycin for intracellular cytokine staining. Percentages of cells expressing IL-17A and IL-22 in gated CD4⁺ and CD8⁺ T cells were determined by flow cytometry. Statistical analysis was performed using Spearman rank correlation. IL = interleukin; LV = lesion volume.

IFN-β-1a treatment of patients with RRMS inhibited Th22, Th1, and Th17, while inducing Th2 cell-related gene expression in CD4⁺ T cells. CD4⁺ T cells from 21 patients with RRMS at baseline and month 6 after IFN-β-1a treatment were separated using magnetic beads. Gene expression of (A) transcription factors, (B) cytokines, and (C) cytokine receptors was measured using quantitative real time–PCR. Results are expressed as the relative gene expression normalized against 18S messenger RNA. Statistical analysis was performed using a paired t test. AHR = aryl hydrocarbon receptor; IFN-β-1a = interferon β-1a; IL = interleukin; RORc = retinoic acid–related orphan nuclear hormone receptor C; RRMS = relapsing-remitting multiple sclerosis.

IFN-β-1a treatment significantly decreased the percentages of IL-22– and IL-17F–producing CD4⁺ T cells (A), and IL-17A– and IL-17F–producing CD8⁺ T cells in patients with RRMS (B). Fresh PBMCs from 21 patients with RRMS at baseline and after 6 months of IFN-β-1a treatment were used for intracellular cytokine staining. The percentages of CD4⁺ or CD8⁺ T cells expressing indicated cytokines were determined by flow cytometry. Statistical analysis was performed using a paired t test. IFN-β-1a = interferon β-1a; IL = interleukin; PBMC = peripheral blood mononuclear cell; RRMS = relapsing-remitting multiple sclerosis.