The suppressive effect of TGF-beta on IL-12-mediated immune modulation specific to a peptide Ac1-11 of myelin basic protein (MBP): a mechanism involved in inhibition of both IL-12 receptor beta1 and beta2.
Transforming growth factor (TGF)-beta exerts a counter-regulatory effect on interleukin (IL)-12-mediated immune modulation. The underlying mechanism is not fully understood. Here we demonstrate that the expression of IL-12Rbeta1 and IL-12Rbeta2 in MBP peptide Ac1-11-primed splenocytes is upregulated upon antigen stimulation. TGF-beta induces an unresponsiveness of these primed splenocytes to IL-12 signaling through a mechanism involved in inhibition of both IL-12Rbeta1 and beta2. The modulation of IL-12Rbeta1 and beta2 expression by Ac1-11 stimulation and TGF-beta is mainly involved in CD4+ population. These data indicate that both IL-12Rbeta1 and IL-12Rbeta2 expression are crucial during T cell activation. TGF-beta-induced inhibition of IL-12R expression will reduce cellular immune responses during IL-12-mediated autoimmune disease.
Xu
H
H
Department of Neurology, University of Pennsylvania Medical Center, 3400 Spruce Street, Philadelphia, PA 19104, USA.
Zhang
G X
GX
Wysocka
M
M
Wu
C Y
CY
Trinchieri
G
G
Rostami
A
A
D000818:Animals; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000037:antagonists & inhibitors* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D004676:Myelin Basic Protein / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D053707:Receptors, Interleukin-12; D013154:Spleen / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*
D001324:Autoantigens; C508440:Il12rb1 protein, mouse; C508443:Il12rb2 protein, mouse; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D016212:Transforming Growth Factor beta; D018664:Interleukin-12; D007371:Interferon-gamma