Summary
The purpose of the study was to observe the effect of rapamycin (RAPA) on the differentiation and maturation of rat bone marrow-derived dendritic cells (BMDCs) in vitro. BMDCs from Wistar rats were cultured with granulocyte-macrophage colony-stimulating factor plus interleukin-4 in the presence or absence of RAPA (20 ng/mL), and stimulated with lipopolysaccharide (LPS) for 24 h before cells and supernatants were collected. Surface phenotype of BMDCs was flow-cytometrically detected to determine the expression of maturation markers, MHC class II and CD86. Supernatants were analyzed for the production of IL-12 and IFN-γ cytokines by using ELISA. BMDCs were co-cultured with T cells from Lewis rats and mixed lymphocyte reaction was assessed by MTT method. The morphology of BMDCs stimulated with LPS remained immature after RAPA pretreatment. RAPA significantly decreased the CD86 expression, impaired the IL-12 and IFN-γ production of BMDCs stimulated with LPS, and inhibited the proliferation of allogeneic T cells. In conclusion, RAPA can inhibit the maturation of BMDCs stimulated with LPS in terms of the morphology, surface phenotype, cytokine production, and ability of BMDCs to stimulate the proliferation of allogeneic T cells in vitro.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Banchereau J, Briere F, Caux C et al. Immunobiology of dendritic cells. Annu Rev Immunol, 2000,18:767–811
Banchereau J, Steinman R M. Dendritic cells and the control of immunity. Nature, 1998,392:245–252
Reis e Sousa C. Dendritic cells in a mature age. Nat Rev Immunol, 2006,6(6):476–483
Steinman R M, Hawiger D, Nussenzweig M C. Tolerogenic dendritic cells. Annu Rev Immunol, 2003,21: 685–711
Jonuleit H, Schmitt E, Schuler G et al. Induction of interleukin 10-producing, non-proliferating CD4(+) T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. J Exp Med, 2000,192:1213–1222
Fu F, Li Y, Qian S et al. Costimulatory molecule-deficient dendritic cell progenitors (MHC class II+, CD80dim, CD86−) prolong cardiac allograft survival in nonimmunosuppressed recipients. Transplantation, 1996,62:659–665
Dhodapkar M V, Steinman R M, Krasovsky J, et al. Antigen-specific inhibition of effector T cell in humans after injection of immature dendritic cells. J Exp Med, 2001,193:233–238
Saunders R N, Metcalfe M S, Nicholson M L et al. Rapamycin in transplantation: a review of the evidence. Kidney Int, 2001,59:3–16
Chan M, Pearson G J. New advances in antirejection therapy. Curr Opin Cardiol, 2007,22(2):117–122
Sigal N H, Dumont F J. Cyclosporin A, FK-506, and rapamycin: pharmacologic probes of lymphocyte signal transduction. Annu Rev Immunol, 1992,10:519–560
Mariotti J, Foley J, Jung U et al. Ex vivo rapamycin generates apoptosis-resistant donor Th2 cells that persist in vivo and prevent hemopoietic stem cell graft rejection. J Immunol, 2008,180(1):89–105
Horibe E K, Sacks J, Unadkat J et al. Rapamycin-conditioned, alloantigen-pulsed dendritic cells promote indefinite survival of vascularized skin allografts in association with T regulatory cell expansion. Transpl Immunol, 2008,18(4):307–318
Bertagnolli M M, Yang L, Herrmann S H et al. Evidence that rapamycin inhibits interlerukin-12-induced proliferation of activated T lymphocytes. Transplantation, 1994,58:1091–1096
Aaguaard-Tillery K M and Jelinek D F. Inhibition of human B lymphocyte cell cycle progression and differentiation by rapamycin. Cell Immunol, 1994,156:493–507
Matsue H, Yang C, Matsue K et al. Contrasting impacts of immunosuppressive agents (rapamycin, FK506, cyclosporin A, and dexamethasone) on bidirectional dendritic cell-T cell interaction during antigen presentation. J Immunol, 2002,169:3555–3564
Chiang P H, Wang L, Bonham C A et al. Mechanistic insights into impaired dendritic cell function by rapamycin: Inhibition of Jak2/Stat4 signaling pathway. J Immunol, 2004,172:1355–1363
Hackstein H, Taner T, Zahorchak A F et al. Rapamycin inhibits IL-4-induced dendritic cell maturation in vitro and dendritic cell mobilization and function in vivo. Blood, 2003,101:4457–4463
Woltman A M, de Fijter J W, Kamerling S W et al. Rapamycin induces apoptosis in monocyte-and CD34-derived dendritic cells but not in monocytes and macrophages. Blood, 2001,98:174–180
Monti P, Mercalli A, Leone B E et al. Rapamycin impairs antigen uptake of human dendritic cells. Transplantation, 2003,75:137–145
Taner T, Hackstein H, Wang Z et al. Rapamycin-treated, alloantigen-pulsed host dendritic cells induce ag-specific T cell regulation and prolong graft survival. Am J Transplant, 2005,5:228–236
Murphy K M, Ouyang W, Farrar J D et al. Signaling and transcription in T helper development. Annu Rev Immunol, 2000,18:451–494
Kishimoto K, Dong V M, Sayegh M H. The role of costimulatory molecules as targets for new immunosuppressive in transplantation. Curr Opini Urol, 2000,10(2): 57–62
Macatonia S, Hosken N, Litton M et al. Dendritic cells produce IL-12 and direct the development of Th1 cells from naive CD4+ T cells. J Immunol, 1995,154:5071–5079
Trinchieri G. Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol, 2003,3(2):133–146
Bianchi R, Grohmann U, Vacca C et al. Autocrine IL-12 is involved in dendritic cell modulation via CD40 ligation. J Immunol, 1999,63:2517–2521
Boehm U, Klamp T, Groot M et al. Cellular responses to interferon-gamma. Annu Rev Immunol, 1997,15:749–795
Watanabe H, Unger M, Tuvel B et al. Contact hypersensitivity: the mechanism of immune responses and T cell balance. J Interferon Cytokine Res, 2002,22(4):407–412
Ohteki T, Fukao T, Suzue K et al. Interleukin 12-dependent interferon-γ production by CD8alpha+ lymphoid dendritic cells. J Exp Med, 1999,189:1981–1986
Walzer T, Dalod M, Vivier E et al. Natural killer cell-dendritic cell crosstalk in the initiation of immune responses. Expert Opin Biol Ther, 2005,5(Suppl 1):S49–S59
Stober D, Schirmbeck R, and Reimann J IL-12/IL-18-dependent IFN-γ release by murine dendritic cells. J Immunol, 2001,167:957–965
Author information
Authors and Affiliations
Additional information
Yingjun DING, male, born in 1979, Resident
Dr. Yingjun DING and Dr. Xiang CHENG contributed equally to the project.
This work was supported by grants from the National Basic Research Program of China (973 Program) (No. 2007CB512000, 2007CB512005) and National Natural Science Foundation of China (No. 30600234).
Rights and permissions
About this article
Cite this article
Ding, Y., Cheng, X., Tang, T. et al. Rapamycin modulates the maturation of rat bone marrow-derived dendritic cells. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 28, 391–395 (2008). https://doi.org/10.1007/s11596-008-0405-1
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11596-008-0405-1