Diminished myelin-specific T cell activation associated with increase in CTLA4 and Fas molecules in multiple sclerosis patients treated with IFN-beta.
Multiple sclerosis (MS) is a chronic inflammatory disease of the white matter of the central nervous system (CNS) characterized by focal areas of demyelination. Interferon-beta (IFN-beta) provides an effective treatment that lessens the frequency and severity of exacerbations in relapsing-remitting multiple sclerosis (RRMS), but the mechanisms by which IFN-beta is efficient remain uncertain. The data presented here demonstrate that IFN-beta impairs the proliferative response to myelin basic protein (MBP) and myelin, as well as increasing the expression of the CTLA4 intracellular molecule. Moreover, this treatment increases the expression of surface Fas molecules and of the soluble form of these molecules. Our hypothesis is that the increase in Fas and CTLA4 molecules in MS patients may lead to lymphocyte apoptosis, which suggests possible mechanisms underlying the therapeutic response to IFN-beta.
Hallal-Longo
Dannie E M
DE
Neuroimmunology Unit, Department of Microbiology and Immunology, Biology Institute, University of Campinas, UNICAMP, Campinas SP, Brazil.
Mirandola
Sandra R
SR
Oliveira
Elaine C
EC
Farias
Alessandro S
AS
Pereira
Fernanda G
FG
Metze
Irene L
IL
Brandão
Carlos Otavio
CO
Ruocco
Heloísa H
HH
Damasceno
Benito P
BP
Santos
Leonilda M B
LM
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D060908:CTLA-4 Antigen; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000473:pathology; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000187:drug effects / Q000276:immunology*; D012995:Solubility / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D019014:fas Receptor / Q000097:blood / Q000378:metabolism*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C491901:FAS protein, human; D004676:Myelin Basic Protein; D019014:fas Receptor; D016899:Interferon-beta