cross-regulate antigen presentation to CD4 T cells by macrophages
* Departments of Rheumatology and
Neurology, The Medical School, University of Newcastle upon Tyne, United Kingdom
Correspondence: Dr. John H. Robinson, Department of Rheumatology, The Medical School, University of Newcastle, Framlington Place, Newcastle upon Tyne, NE2 4HH, U.K. E-mail: j.h.robinson{at}ncl.ac.uk
We studied the interaction of transforming growth factor-ß1 (TGF-ß1) and interferon-
(IFN-) in regulating Ag presentation in macrophages. TGF-ß1 blocked, and IFN- 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-ß1 reduced the constitutive expression of MHC class II transactivator (CIITA), MHC class II (MHC-II), invariant chain, and DO mRNA, whereas IFN- 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-ß1 down-regulated IFN--mediated enhancement of antigen presentation and inhibited IFN--inducible CIITA and MHC-II class II mRNA expression. The effect of TGF-ß1 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-ß1 and IFN- 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.
Key Words: cytokines • MHC class II • chaperones • costimulation • Streptococcus pyogenes
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