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Lookup NU author(s): Dr Alexei von Delwig,
Dr Jeong-Jin Lee,
Professor Zofia Chrzanowska-Lightowlers,
Professor John Robinson
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We studied the interaction of transforming growth factor-β1 (TGF-β1) and interferon-γ (IFN-γ) in regulating Ag presentation in macrophages. TGF-β1 blocked, and IFN-γ 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-β1 reduced the constitutive expression of MHC class II transactivator (CIITA), MHC class II (MHC-II), invariant chain, and DO mRNA, whereas IFN-γ up-regulated the expression of CIITA and MHC-II mRNA without affecting in-variant chain or DO mRNA. However, neither cytokine affected DM mRNA expression. Treatment of macrophages with the two cytokines in combination showed that TGF-β1 down-regulated IFN-γ-mediated enhancement of antigen presentation and inhibited IFN-γ-inducible CIITA and MHC-II class II mRNA expression. The effect of TGF-β1 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-β1 and IFN-γ 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.
Author(s): von Delwig A, Lee JJ, Chrzanowska-Lightowlers ZMA, Robinson JH
Publication type: Article
Publication status: Published
Journal: Journal of Leukocyte Biology
ISSN (print): 0741-5400
Publisher: Federation of American Societies for Experimental Biology
PubMed id: 12101276