Single-cell analysis of cytokine production shows different immune profiles in multiple sclerosis patients with active or quiescent disease.
Peripheral blood mononuclear cells of multiple sclerosis (MS) patients were stimulated with myelin basic protein (MBP) together with anti-CD28 monoclonal antibody and staphylococcal enterotoxin B to optimize cytokine production by antigen-specific cells. Type 1 (IL-2, IL-12, IFNgamma) and pro-inflammatory (TNFalpha, IL-1beta, IL-6) cytokines were augmented in CD4+, CD8+, and CD14+ cells of acute MS patients and of patients undergoing disease reactivation. These cytokines were reduced in IFNbeta-treated and in stable MS patients; type 2 cytokines (IL-4, IL-10) were increased in these patients. Similar immune profiles are seen in MS patients in whom remission is naturally or pharmacologically (IFNbeta) achieved. Cytokine alterations are particularly evident in CD14+ cells, underlying their critical role in the modulation of the immune response.
Clerici
M
M
Cattedra di Immunologia, Università degli Studi di Milano, DISP LITA Vialba, Via G.B. Grassi, 74, 20157, Milan, Italy. mago@mailserver.unimi.it
Saresella
M
M
Trabattoni
D
D
Speciale
L
L
Fossati
S
S
Ruzzante
S
S
Cavaretta
R
R
Filippi
M
M
Caputo
D
D
Ferrante
P
P
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018106:CD28 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D004768:Enterotoxins / Q000494:pharmacology; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D066298:In Vitro Techniques; D016899:Interferon-beta / Q000627:therapeutic use; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007375:Interleukin-1 / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000276:immunology*; D004676:Myelin Basic Protein / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D016207:Cytokines; D004768:Enterotoxins; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D004676:Myelin Basic Protein; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; C031818:enterotoxin B, staphylococcal; D016899:Interferon-beta; D007371:Interferon-gamma