TGF-beta1 and IFN-gamma cross-regulate antigen presentation to CD4 T cells by macrophages.
We studied the interaction of transforming growth factor-beta1 (TGF-beta1) and interferon-gamma (IFN-gamma) in regulating Ag presentation in macrophages. TGF-beta1 blocked, and IFN-gamma enhanced Ag presentation of two T cell epitopes from the group A streptococcal M protein processed from viable Streptococcus pyogenes. Consistent with the functional data, TGF-beta1 reduced the constitutive expression of MHC class II transactivator (CIITA), MHC class II (MHC-II), invariant chain, and DO mRNA, whereas IFN-gamma up-regulated the expression of CIITA and MHC-II mRNA without affecting invariant chain or DO mRNA. However, neither cytokine affected DM mRNA expression. Treatment of macrophages with the two cytokines in combination showed that TGF-beta1 down-regulated IFN-gamma-mediated enhancement of antigen presentation and inhibited IFN-gamma-inducible CIITA and MHC-II class II mRNA expression. The effect of TGF-beta1 on Ag presentation was shown to be independent of the surface expression of CD80, CD86, or CD40 costimulatory molecules by flow cytometry. Our results show that TGF-beta1 and IFN-gamma cross-regulate Ag presentation by influencing the transcription of several genes associated with antigen presentation function, which may represent an important mechanism limiting T cell activation during an immune response.
Delvig
Alexei A
AA
Department of Rheumatology, The Medical School, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
Lee
Jeong J
JJ
Chrzanowska-Lightowlers
Zosia M A
ZM
Robinson
John H
JH
D000818:Animals; D017951:Antigen Presentation; D000942:Antigens, Bacterial; D015703:Antigens, CD / Q000096:biosynthesis; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology; D002460:Cell Line; D005786:Gene Expression Regulation; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000235:genetics; D006825:Hybridomas; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007700:Kinetics; D008213:Lymphocyte Activation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D018832:Molecular Chaperones / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
D000942:Antigens, Bacterial; D015703:Antigens, CD; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D000949:Histocompatibility Antigens Class II; D018832:Molecular Chaperones; D012333:RNA, Messenger; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C014689:streptococcal M protein; D007371:Interferon-gamma