Treatment with type I interferons induces a regulatory T cell subset in peripheral blood mononuclear cells from multiple sclerosis patients.
Type I Interferon (IFN-alpha/beta) therapy has altered the natural course of multiple sclerosis. In this paper we evaluate the possible molecular mechanisms involved in the in vitro effects of IFN-alpha/beta on peripheral blood mononuclear cells from patients with clinically definite Relapsing-Remitting Multiple Sclerosis. The total RNA from IFN-alpha, IFN-beta treated cells and untreated cells was extracted and amplified for CD86, CD28, CTLA-4, TNF-alpha, IFN-gamma, CCL2, CCR5, IL-13, MMP-9, TIMP-1, CD25, TGF-beta, IL-10 and the transcriptional factor Foxp3 by Reverse Transcription-Polymerase Chain Reaction and the CD4+CD25high subset was evaluated using flow cytometry. In general, there were no significant differences concerning the modulation of the genes studied in the response to IFN-alpha and IFN-beta treatments, which suggest a similar mechanism of action for both interferons. However, we found a significant increment in IFN-gamma expression after IFN-alpha but not after IFN-beta treatments. The in vitro treatment of mononuclear cells from multiple sclerosis patients with both interferons significantly increased the CD25 mRNA. Furthermore, we observed a CD25/Foxp3 correlation and an increment of the CD4+CD25high subset, indicating that the induction of regulatory T cells could be a crucial mechanism involved in the type I interferon effects.
Pentón-Rol
G
G
Clinical Trials Division, Center for Biological Research, PO. Box: 6332, Havana 10 600, Cuba. giselle.penton@cigb.edu.cu
Cervantes-Llanos
M
M
Cabrera-Gómez
J A
JA
Alonso-Ramírez
R
R
Valenzuela-Silva
C
C
Rodríguez-Lara
R
R
Montero-Casimiro
E
E
Bello-Rivero
I
I
López-Saura
P
P
D017951:Antigen Presentation; D001812:Blood-Brain Barrier; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007370:Interferon Type I / Q000276:immunology* / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D007370:Interferon Type I