Endogenous and recombinant type I interferons and disease activity in multiple sclerosis.
Although treatment of multiple sclerosis (MS) with the type I interferon (IFN) IFN-β lowers disease activity, the role of endogenous type I IFN in MS remains controversial. We studied CD4+ T cells and CD4+ T cell subsets, monocytes and dendritic cells by flow cytometry and analysed the relationship with endogenous type I IFN-like activity, the effect of IFN-β therapy, and clinical and magnetic resonance imaging (MRI) disease activity in MS patients. Endogenous type I IFN activity was associated with decreased expression of the integrin subunit CD49d (VLA-4) on CD4+CD26(high) T cells (Th1 helper cells), and this effect was associated with less MRI disease activity. IFN-β therapy reduced CD49d expression on CD4+CD26(high) T cells, and the percentage of CD4+CD26(high) T cells that were CD49d(high) correlated with clinical and MRI disease activity in patients treated with IFN-β. Treatment with IFN-β also increased the percentage of CD4+ T cells expressing CD71 and HLA-DR (activated T cells), and this was associated with an increased risk of clinical disease activity. In contrast, induction of CD71 and HLA-DR was not observed in untreated MS patients with evidence of endogenous type IFN I activity. In conclusion, the effects of IFN-β treatment and endogenous type I IFN activity on VLA-4 expression are similar and associated with control of disease activity. However, immune-activating effects of treatment with IFN-β may counteract the beneficial effects of treatment and cause an insufficient response to therapy.
Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. sellebjerg@dadlnet.dk
Finn
F
Sellebjerg
Martin
M
Krakauer
Signe
S
Limborg
Dan
D
Hesse
Henrik
H
Lund
Annika
A
Langkilde
Helle Bach
HB
Søndergaard
Per Soelberg
PS
Sørensen
D000328:Adult; D015703:Antigens, CD / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells; D003718:Denmark; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D039441:Integrin alpha4 / Q000276:immunology; D007370:Interferon Type I / Q000276:immunology*; D016899:Interferon-beta / Q000276:immunology* / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009000:Monocytes; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D011990:Receptors, Transferrin / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology*; D018709:Statistics, Nonparametric; D016176:T-Lymphocyte Subsets / Q000276:immunology
D015703:Antigens, CD; C068126:CD71 antigen; D006684:HLA-DR Antigens; D007370:Interferon Type I; D011990:Receptors, Transferrin; D011994:Recombinant Proteins; D039441:Integrin alpha4; D016899:Interferon-beta