Production of TGF-β1 as a Mechanism for Defective Antigen-presenting Cell Function of Macrophages Generated in vitro with M-CSF
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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-β1 by BM-Mp. Methods: Microarray analysis showed that TGF-β1 was highly expressed in BM-Mp, compared to a macrophage cell line, B6D, which exerted efficient APC function. Production of TGF-β1 by BM-Mp was confirmed by neutralization experiments of TGF-β1 as well as by real time-polymerase chain reaction (PCR). Results: Addition of anti-TGF-β1 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-β1. Quantitative real time-PCR analysis also confirmed the enhanced expression of TGF-β1 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-β1 by macrophages.
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-β1 by BM-Mp. Methods: Microarray analysis showed that TGF-β1 was highly expressed in BM-Mp, compared to a macrophage cell line, B6D, which exerted efficient APC function. Production of TGF-β1 by BM-Mp was confirmed by neutralization experiments of TGF-β1 as well as by real time-polymerase chain reaction (PCR). Results: Addition of anti-TGF-β1 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-β1. Quantitative real time-PCR analysis also confirmed the enhanced expression of TGF-β1 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-β1 by macrophages.
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