T cell response to myelin basic protein before and after treatment with interferon beta in multiple sclerosis.
Studies on the in vivo effects of interferon-beta (IFNbeta) therapy on autoreactive T cells have never been carried out in multiple sclerosis (MS). We investigated the T cell response to myelin basic protein (MBP), before and after IFN-beta therapy, raising MBP-specific T cell lines (TCL) from the peripheral blood of six MS patients with a satisfactory response to the treatment. IFNbeta did not affect the relative frequency and epitope specificity of the TCL. After IFNbeta therapy, the production of interleukin-4 was decreased in MBP-stimulated TCL while the secretion of interferon-gamma was increased in unstimulated TCL. Interleukin-10 and tumor necrosis factor-alpha did not show significant variations. This finding supports recent suggestions about the complexity of the T helper 1/T helper 2 paradigm in MS and other organ-specific autoimmune diseases. In fact, the beneficial effects of IFNbeta do not exclude an immunostimulatory action that may involve potentially autoreactive T cells. This has implications for future treatment options, including combination therapies.
Ristori
G
G
Department of Neurological Sciences, Università La Sapienza, Rome, Italy. md0914@mclink.it
Montesperelli
C
C
Gasperini
C
C
Battistini
L
L
Borsellino
G
G
Buttinelli
C
C
Cannoni
S
S
Perna
A
A
Pozzilli
C
C
Salvetti
M
M
D000328:Adult; D001327:Autoimmune Diseases / Q000276:immunology* / Q000628:therapy; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016899:Interferon-beta / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D009103:Multiple Sclerosis / Q000276:immunology* / Q000628:therapy; D004676:Myelin Basic Protein / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007155:Immunologic Factors; D004676:Myelin Basic Protein; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D016899:Interferon-beta; D007371:Interferon-gamma