Production of TGF-beta1 as a Mechanism for Defective Antigen-presenting Cell Function of Macrophages Generated in vitro with M-CSF.
- Author:
Jae Kwon LEE
1
;
Young Ran LEE
;
Young Hee LEE
;
Kyungjae KIM
;
Chong Kil LEE
Author Information
- Publication Type:In Vitro ; Original Article
- Keywords: macrophage; M-CSF; APC function; TGF-beta1
- MeSH: Antigen-Presenting Cells; Bone Marrow Cells; Cell Line; Histocompatibility; Interleukin-6; Interleukins; Macrophage Colony-Stimulating Factor; Macrophages; Microarray Analysis; T-Lymphocytes; Transforming Growth Factor beta1
- From:Immune Network 2009;9(1):27-33
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND: Macrophages generated in vitro using macrophage-colony stimulating factor (M-CSF) and interleukin (IL)-6 from bone marrow cells (BM-Mp) are defective in antigen presenting cell (APC) function as shown by their ability to induce the proliferation of anti-CD3 mAb-primed syngeneic T cells. However, they do express major histocompatibility (MHC) class I and II molecules, accessory molecules and intracellular adhesion molecules. Here we demonstrate that the defective APC function of macrophages is mainly due to production of TGF-beta1 by BM-Mp. METHODS: Microarray analysis showed that TGF-beta1 was highly expressed in BM-Mp, compared to a macrophage cell line, B6D, which exerted efficient APC function. Production of TGF-beta1 by BM-Mp was confirmed by neutralization experiments of TGF-beta1 as well as by real time-polymerase chain reaction (PCR). RESULTS: Addition of anti-TGF-beta1 monoclonal antibody to cultures of BM-Mp and anti-CD3 mAb-primed syngeneic T cells efficiently induced the proliferation of syngeneic T cells. Conversely, the APC function of B6D cells was almost completely suppressed by addition of TGF-beta1. Quantitative real time-PCR analysis also confirmed the enhanced expression of TGF-beta1 in BM-Mp. CONCLUSION: The defective APC function of macrophages generated in vitro with M-CSF and IL-6 was mainly due to the production of TGF-beta1 by macrophages.