[Transforming growth factor-beta 1 inhibits the generation of dendritic cells from murine hematopoietic progenitor cells in vitro].

OBJECTIVE

To investigate the regulatory effect of transforming growth factor-beta 1 (TGF-beta 1) on the generation of dendritic cells (DCs) from hematopoietic progenitor cells (HPCs) and its cellular and molecular mechanisms.

METHODS

Murine bone marrow derived-Lin c-kit+ HPCs were isolated by a cell sorter and cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF), stem cell factor (SCF), tumor necrosis factor alpha(TNF alpha) and TGF-beta 1. The generation of DC precursors and mature DCs and their phenotypes were analyzed by a cell sorter, reverse transcription-polymerase chain reaction (RT-PCR), and allogenic mixed lymphocyte reaction (MLR).

RESULTS

TGF-beta 1 could significantly inhibit the generation of DC precursors at day 6 and mature DCs at day 12 from murine Lin- c-kit+ HPCs stimulated with GM-CSF + SCF + TNF alpha or GM-CSF + SCF. Moreover, TGF-beta 1 markedly suppressed the expression of antigen peresenting molecule Ia and co-stimulatory molecule CD86 on the surface of cultured Lin- c-kit+ HPCs. Examination of RT-PCR showed that TGF-beta 1 could also inhibit the expression of MHC class II trans-activator (CTIIA) mRNA, which encodes a transcriptional factor to strictly control the expression of MHC class II antigens in the cultured cells.

CONCLUSION

Our results suggest that TGF-beta 1 is an inhibitory cytokine for the generation of DC precursors and maturation of DC from HPCs, which may account for the cellular mechanisms of TGF-beta 1-mediated immuno-suppressive functions in vivo and in vitro.