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TGF‐β1 and IFN‐γ cross‐regulate antigen presentation to CD4 T cells by macrophages
Author(s) -
Delvig Alexei A.,
Lee Jeong J.,
ChrzanowskaLightowlers Zosia M. A.,
Robinson John H.
Publication year - 2002
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.72.1.163
Subject(s) - ciita , biology , antigen presentation , mhc class ii , antigen processing , cd80 , cd74 , cd40 , antigen presenting cell , cytokine , major histocompatibility complex , antigen , mhc restriction , immune system , t cell , microbiology and biotechnology , immunology , cytotoxic t cell , in vitro , biochemistry
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 invariant 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.