TNF-α Promotes IFN-γ-Induced CD40 Expression and Antigen Process in Myb-Transformed Hematological Cells

Tumour necrosis factor-α, interferon-γ and interleukin-4 are critical cytokines in regulating the immune responses against infections and tumours. In this study, we investigated the effects of three cytokines on CD40 expression in Myb-transformed hematological cells and their regulatory roles in promoting these cells into dendritic cells. We observed that both interleukin-4 and interferon-γ increased CD40 expression in these hematological cells in a dose-dependent manner, although the concentration required for interleukin-4 was significantly higher than that for interferon-γ. We found that tumour necrosis factor-α promoted CD40 expression induced by interferon-γ, but not by interleukin-4. Our data showed that tumour necrosis factor-α plus interferon-γ-treated Myb-transformed hematological cells had the greatest ability to take up and process the model antigen DQ-Ovalbumin. Tumour necrosis factor-α also increased the ability of interferon-γ to produce the mixed lymphocyte reaction to allogenic T cells. Furthermore, only cotreatment with tumour necrosis factor-α and interferon-γ induced Myb-transformed hematological cells to express interleukin-6. These results suggest that tumour necrosis factor-α plays a key regulatory role in the development of dendritic cells from hematological progenitor cells induced by interferon-γ.

[1]  D. Broering,et al.  TNF-alpha similarly induces IL-6 and MCP-1 in fibroblasts from colorectal liver metastases and normal liver fibroblasts. , 2010, Biochemical and biophysical research communications.

[2]  M. Moser,et al.  DC subsets in positive and negative regulation of immunity , 2010, Immunological reviews.

[3]  E. Clark,et al.  The role of CD40 and CD154/CD40L in dendritic cells. , 2009, Seminars in immunology.

[4]  J. Isaacs,et al.  Tumour necrosis factor alpha blockade impairs dendritic cell survival and function in rheumatoid arthritis , 2009, Annals of the rheumatic diseases.

[5]  S. Singer,et al.  Phosphoinositide 3-Kinase-Dependent Inhibition of Dendritic Cell Interleukin-12 Production by Giardia lamblia , 2008, Infection and Immunity.

[6]  H. Ueno,et al.  Dendritic Cells: A Critical Player in Cancer Therapy? , 2008, Journal of immunotherapy.

[7]  D. Meldrum,et al.  Differential IL-6 and VEGF secretion in adult and neonatal mesenchymal stem cells: role of NFkB. , 2008, Cytokine.

[8]  J. Dausset,et al.  Modulation of dendritic cell differentiation by HLA-G and ILT4 requires the IL-6—STAT3 signaling pathway , 2008, Proceedings of the National Academy of Sciences.

[9]  E. Shpall,et al.  Deficient TH-1 Responses From TNF-α–matured and α-CD40–matured Dendritic Cells , 2008, Journal of immunotherapy.

[10]  H. Ueno,et al.  Taming cancer by inducing immunity via dendritic cells , 2007, Immunological reviews.

[11]  R. Steinman,et al.  Taking dendritic cells into medicine , 2007, Nature.

[12]  A. Šedivá,et al.  Impaired Toll-like receptor 8-mediated IL-6 and TNF-alpha production in antigen-presenting cells from patients with X-linked agammaglobulinemia. , 2007, Blood.

[13]  Chekhun Vf,et al.  Expression of CD40 and CD40L on tumor cells: the role of their interaction and new approach to immunotherapy. , 2007 .

[14]  L. Zitvogel,et al.  Dendritic cell derived‐exosomes: biology and clinical implementations , 2006, Journal of leukocyte biology.

[15]  X. Yang,et al.  Effect of 15d-PGJ2 on the Expression of CD40 and RANTES Induced by IFN-γ and TNF-α on Renal Tubular Epithelial Cells (HK-2) , 2006, American Journal of Nephrology.

[16]  K. Iwabuchi,et al.  Low-dose lipopolysaccharide modifies the production of IL-12 by dendritic cells in response to various cytokines. , 2006, Journal of clinical and experimental hematopathology : JCEH.

[17]  I. Frazer,et al.  Gene Codon Composition Determines Differentiation-Dependent Expression of a Viral Capsid Gene in Keratinocytes In Vitro and InVivo , 2005, Molecular and Cellular Biology.

[18]  M. Harnett.  CD40: A Growing Cytoplasmic Tale , 2004, Science's STKE.

[19]  J. Gumperz.  Antigen specificity of semi‐invariant CD1d‐restricted T cell receptors: The best of both worlds? , 2004, Immunology and cell biology.

[20]  H. Um,et al.  TNF‐α suppresses dendritic cell death and the production of reactive oxygen intermediates induced by plasma withdrawal , 2004, Experimental dermatology.

[21]  K. Schroder,et al.  Interferon- : an overview of signals, mechanisms and functions , 2004 .

[22]  A. Palucka,et al.  TNF Skews Monocyte Differentiation from Macrophages to Dendritic Cells 1 , 2003, The Journal of Immunology.

[23]  Ranjeny Thomas,et al.  Recent advances on the role of CD40 and dendritic cells in immunity and tolerance , 2003, Current opinion in hematology.

[24]  L. Tailleux,et al.  CD40 ligation and phagocytosis differently affect the differentiation of monocytes into dendritic cells , 2002, Journal of leukocyte biology.

[25]  B. Winston,et al.  Complement Factor B Gene Regulation: Synergistic Effects of TNF-α and IFN-γ in Macrophages1 , 2002, The Journal of Immunology.

[26]  M. Ritter,et al.  Optimal analysis of composite cytokine responses during alloreactivity. , 2002, Journal of immunological methods.

[27]  V. Nguyen,et al.  IL-4-Activated STAT-6 Inhibits IFN-γ-Induced CD40 Gene Expression in Macrophages/Microglia1 , 2000, The Journal of Immunology.

[28]  J. Banyer,et al.  Myb‐transformed hematopoietic cells as a model for monocyte differentiation into dendritic cells and macrophages , 1999, Journal of leukocyte biology.

[29]  R. Ransohoff,et al.  Tumor necrosis factor-alpha signals to the IFN-gamma receptor complex to increase Stat1alpha activation. , 1999, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[30]  V. Nguyen,et al.  Post‐transcriptional inhibition of CD40 gene expression in microglia by transforming growth factor‐β , 1998, European journal of immunology.

[31]  Laurence Zitvogel,et al.  Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell derived exosomes , 1998, Nature Medicine.

[32]  R. Steinman,et al.  Dendritic cells and the control of immunity , 1998, Nature.

[33]  R. Pine.  Convergence of TNFα and IFNγ signalling pathways through synergistic induction of IRF-1/ISGF-2 is mediated by a composite GAS/κB promoter element , 1997 .

[34]  P. Kalinski,et al.  IL-12-deficient dendritic cells, generated in the presence of prostaglandin E2, promote type 2 cytokine production in maturing human naive T helper cells. , 1997, Journal of immunology.

[35]  Yoshihiro Ohmori,et al.  Synergy between Interferon-γ and Tumor Necrosis Factor-α in Transcriptional Activation Is Mediated by Cooperation between Signal Transducer and Activator of Transcription 1 and Nuclear Factor κB* , 1997, The Journal of Biological Chemistry.

[36]  G. Brunob,et al.  Parietaria judaica–specific T-cell clones from atopic patients: Heterogeneity in restriction, Vβ usage, and cytokine profile , 1996 .

[37]  L. Ashman,et al.  Enforced expression of full length c-Myb leads to density-dependent transformation of murine haemopoietic cells. , 1995, Oncogene.

[38]  G. Pauli,et al.  Spontaneous apoptosis of dendritic cells is efficiently inhibited by TRAP (CD40‐ligand) and TNF‐α, but strongly enhanced by interleukin‐10 , 1995, European journal of immunology.

[39]  Y. Ohmori,et al.  The interferon-stimulated response element and a kappa B site mediate synergistic induction of murine IP-10 gene transcription by IFN-gamma and TNF-alpha. , 1995, Journal of immunology.

[40]  A. Jahnke,et al.  Synergistic activation of intercellular adhesion molecule 1 (ICAM‐1) by TNF‐α and IFN‐γ is mediated by p65/p50 and p65/c‐Rel and interferon‐responsive factor Statlα (p91) that can be activated by both IFN‐γ and IFN‐α , 1994 .

[41]  T. Gonda,et al.  Differentiation state and responses to hematopoietic growth factors of murine myeloid cells transformed by myb. , 1993, Blood.

[42]  H. Baumann,et al.  Leukemia inhibitory factor, interferon gamma and dexamethasone regulate N-glycosylation of alpha 1-protease inhibitor in human hepatoma cells. , 1993, European journal of cell biology.

[43]  G. Hansson,et al.  MHC class II antigen expression in human vascular smooth muscle cells is induced by interferon-gamma and modulated by tumour necrosis factor and lymphotoxin. , 1990, Immunology.

[44]  T. Taniguchi,et al.  Induction of the transcription factor IRF-1 and interferon-beta mRNAs by cytokines and activators of second-messenger pathways. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[45]  R L Kassel,et al.  An endotoxin-induced serum factor that causes necrosis of tumors. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[46]  Y. Lebranchu,et al.  CD40 engagement strongly induces CD25 expression on porcine dendritic cells and polarizes the T cell immune response toward Th1. , 2009, Molecular immunology.

[47]  S. White,et al.  RNAi-mediated chromatin silencing in fission yeast. , 2008, Current topics in microbiology and immunology.

[48]  V. Chekhun,et al.  Expression of CD40 and CD40L on tumor cells: the role of their interaction and new approach to immunotherapy. , 2007, Experimental oncology.

[49]  R. Steinman,et al.  Dendritic cells: translating innate to adaptive immunity. , 2006, Current topics in microbiology and immunology.

[50]  J. Banchereau,et al.  Dendritic Cells: A Link Between Innate and Adaptive Immunity , 2004, Journal of Clinical Immunology.

[51]  S. Thomson,et al.  Combinations of IFN-γand IL-4 induce distinct profiles of dendritic cell-associated immunoregulatory properties , 2003, Genes and Immunity.

[52]  Ranjeny Thomas,et al.  CD40 and dendritic cell function. , 2003, Critical reviews in immunology.

[53]  M. Shurin,et al.  TNF-α protects dendritic cells from prostate cancer-induced apoptosis , 2001, Prostate Cancer and Prostatic Diseases.