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

J Neuroimmunol. 2000 Aug 1;108(1-2):53-63. doi: 10.1016/s0165-5728(00)00278-2.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autoantigens / immunology
  • Autoimmune Diseases / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Female
  • Gene Expression Regulation / drug effects
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Interleukin-12 / antagonists & inhibitors*
  • Interleukin-12 / immunology
  • Lymphocyte Activation / drug effects
  • Mice
  • Mice, Inbred Strains
  • Myelin Basic Protein / immunology*
  • Peptide Fragments / immunology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Interleukin / antagonists & inhibitors*
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin / metabolism
  • Receptors, Interleukin-12
  • Spleen / immunology
  • Transforming Growth Factor beta / antagonists & inhibitors
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta / pharmacology*

Substances

  • Autoantigens
  • Il12rb1 protein, mouse
  • Il12rb2 protein, mouse
  • Myelin Basic Protein
  • Peptide Fragments
  • RNA, Messenger
  • Receptors, Interleukin
  • Receptors, Interleukin-12
  • Transforming Growth Factor beta
  • Interleukin-12
  • Interferon-gamma