Similar articles

Abstract: Objective: To explore the effects of transforming growth factor β1 (TGF-β1) on dendritic cells (DC). Methods: Murine bone marrow cells were cultured with GM-CSF and TGF-β1 to develop TGF-β1-treated DC (TGFβ-DC). Then they were stimulated by lipopolysaccharide (LPS). Their phenotypes were assessed by flow cytometry (FCM). The allogeneic stimulating capacity of DC was measured by mixed lymphocyte reaction (MLR) using BrdU ELISA method and IL-12p70 protein was detected by ELISA. The expression of toll-like receptor 4 (TLR4) was analyzed by semi quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and FCM. Results: Compared to immature DC (imDC) cultured by GM-CSF alone, the TGFβ-DC express lower CD80, CD86, I-A^b and CD40. The TGFβ-DC were resistant to maturation with LPS. Maturation resistance was evident from a failure to up-regulate co-stimulatory molecules (CMs), to stimulate larger T cells proliferation and to enhance secretion of IL-12p70. We also found that TGF-β1 could down-regulate TLR4 expression on TGFβ-DC. Conclusion: TGFβ-DC are resistant to maturation stimulus (LPS) and might have some correlation with the down-modulation of TLR4 expression.

[1] Banchereau, J., Steinman, R.M., 1998. Dendritic cells and the control of immunity. Nature, 392:245-252.

[2] Berer, A., Stockl, J., Majdic, O., Wagner, T., Kollars, M., Lechner, K., Geissler, K., Oehler, L., 2000. 1,25-Dihydroxyvitamin D3 inhibits dendritic cell differentiation and maturation in vitro. Exp. Hematol., 28:575-583.

[3] Hackstein, H., Morelli, A.E., Thomson, A.W., 2001. Designer dendritic cells for tolerance induction: guided not misguided missiles. Trends. Immunol., 22:437-442.

[4] Hirano, A., Luke, P.P., Specht, S.M., Fraser, M.O., Takayama, T., Lu, L., Hoffman, R., Thomson, A.W., Jordan, M.L., 2000. Graft hyporeactivity induced by immature donor-derived dendritic cells. Transpl. Immunol., 8:161-168.

[5] Jonuleit, H., Schmitt, E., Steinbrink, K., Enk, A.H., 2001. Dendritic cells as a tool to induce anergic and regulatory T cells. Trends. Immunol., 22:394-400.

[6] Liu, T., Matsuguchi, T., Tsuboi, N., Yajima, T., Yoshikai, Y., 2002. Differences in expression of toll-like receptors and their reactivities in dendritic cells in BALB/c and C57BL/6 mice. Infect. Immun., 70:6638-6645.

[7] Kadowaki, N., Ho, S., Antonenko, S., Malefyt, R.W., Kastelein, R.A., Bazan, F., Liu, Y.J., 2001. Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens. J. Exp. Med., 194:863-869.

[8] Min, W.P., Gorczynski, R., Huang, X.Y., Kushida, M., Kim, P., Obataki, M., Lei, J., Suri, R.M., Cattral, M.S., 2000. Dendritic cells genetically engineered to express Fas ligand induce donor-specific hyporesponsiveness and prolong allograft survival. J. Immunol., 164:161-167.

[9] Moustakas, A., Pardali, K., Gaal, A., Heldin, C.H., 2002. Mechanisms of TGF-beta signaling in regulation of cell growth and differentiation. Immunol. Lett., 82:85-91.

[10] Steinbrink, K., Wolfl, M., Jonuleit, H., Knop, J., Enk, A.H., 1997. Induction of tolerance by IL-10-treated dendritic cells. J. Immunol., 159:4772-4780.

[11] Steinman, R.M., Hawiger, D., Nussenzweig, M.C., 2003. Tolerogenic dendritic cells. Annu. Rev. Immunol., 21:685-711.

[12] Takeuchi, J., Watari, E., Shinya, E., Norose, Y., Matsumoto, M., Seya, T., Sugita, M., Kawana, S., Takahashi, H., 2003. Down-regulation of Toll-like receptor expression in monocyte-derived Langerhans cell-like cells: implications of low-responsiveness to bacterial components in the epidermal Langerhans cells. Biochem. Biophys. Res. Commun., 306:674-679.

[13] Zhang, H., Tay, P.N., Cao, W., Li, W., Lu, J., 2002. Integrin-nucleated Toll-like receptor (TLR) dimerization reveals subcellular targeting of TLRs and distinct mechanisms of TLR4 activation and signaling. FEBS. Lett., 532:171-176.