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
This article has been cited by other articles:
 |
|
 |
|
  M. Francois, R. Romieu-Mourez, S. Stock-Martineau, M.-N. Boivin, J. L. Bramson, and J. Galipeau Mesenchymal stromal cells cross-present soluble exogenous antigens as part of their antigen-presenting cell properties Blood, September 24, 2009; 114(13): 2632 - 2638. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Zhu, Y. Bando, S. Xiao, K. Yang, A. C. Anderson, V. K. Kuchroo, and S. J. Khoury CD11b+Ly-6Chi Suppressive Monocytes in Experimental Autoimmune Encephalomyelitis J. Immunol., October 15, 2007; 179(8): 5228 - 5237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Jelinek, V. Laszlo, E. Buzas, E. Pallinger, B. Hangya, Z. Horvath, and A. Falus Increased antigen presentation and Th1 polarization in genetically histamine-free mice Int. Immunol., January 1, 2007; 19(1): 51 - 58. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Schweitzer, A. M. Reding, H. M. Patton, T. P. Sullivan, C. E. Stubbs, E. Villalobos-Menuey, S. A. Huber, and M. K. Newell Endogenous versus exogenous fatty acid availability affects lysosomal acidity and MHC class II expression J. Lipid Res., November 1, 2006; 47(11): 2525 - 2537. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. B. Arruda, D. Sim, P. R. Chikhlikar, M. Maciel Jr, K. Akasaki, J. T. August, and E. T. A. Marques Dendritic Cell-Lysosomal-Associated Membrane Protein (LAMP) and LAMP-1-HIV-1 Gag Chimeras Have Distinct Cellular Trafficking Pathways and Prime T and B Cell Responses to a Diverse Repertoire of Epitopes J. Immunol., August 15, 2006; 177(4): 2265 - 2275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. T. Chang, J. J. Linderman, and D. E. Kirschner Multiple mechanisms allow Mycobacterium tuberculosis to continuously inhibit MHC class II-mediated antigen presentation by macrophages PNAS, March 22, 2005; 102(12): 4530 - 4535. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. L. Oleszak, J. R. Chang, H. Friedman, C. D. Katsetos, and C. D. Platsoucas Theiler's Virus Infection: a Model for Multiple Sclerosis Clin. Microbiol. Rev., January 1, 2004; 17(1): 174 - 207. [Abstract] [Full Text] [PDF]
|
|
