Cutting Edge: Resistance to Apoptosis and Continuous Proliferation of Dendritic Cells Deficient for TNF Receptor-11

The individual roles of the two TNFRs on dendritic cells (DC) are poorly understood. Investigating bone marrow-derived DC from TNFR-deficient mice, we found that cultures from TNFR1−/− mice continue to form proliferating clusters for 6–9 mo. In contrast, DC derived from wild-type, TNFR2−/−, or TNFR1/2−/− mice survived for only 3–4 wk. DC obtained from these TNFR1−/− long term cultures (LTC) mice show an unusual mixed immature/mature phenotype. The continuous proliferation of the LTC is GM-CSF dependent and correlates with decreased protein levels of the cyclin-dependent kinase inhibitors p27KIP1 and p21CIP1. Prolonged survival of TNFR1−/− DC appears to be independent from NF-κB and Bcl-2 pathways and is rather enabled by the down-regulation of CD95, resulting in the resistance to CD95 ligand-induced apoptosis. These data point to proapoptotic signals mediated via TNFR1 and antiapoptotic signals mediated via TNFR2 in DC.

[1]  K. Elkon,et al.  Dendritic cells are resistant to apoptosis through the Fas (CD95/APO-1) pathway. , 1999, Journal of immunology.

[2]  B. Ryffel,et al.  Migration of Langerhans cells and dermal dendritic cells in skin organ cultures: augmentation by TNF‐α and IL‐1 β , 1999, Journal of leukocyte biology.

[3]  R. Hakem,et al.  Gene targeting in the analysis of mammalian apoptosis and TNF receptor superfamily signaling , 1999, Immunological reviews.

[4]  George Kollias,et al.  On the role of tumor necrosis factor and receptors in models of multiorgan failure, rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease , 1999, Immunological reviews.

[5]  G. Schuler,et al.  An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow. , 1999, Journal of immunological methods.

[6]  C. Rauch,et al.  Tumoricidal activity of tumor necrosis factor–related apoptosis–inducing ligand in vivo , 1999, Nature Medicine.

[7]  Y. Goltsev,et al.  Tumor necrosis factor receptor and Fas signaling mechanisms. , 1999, Annual review of immunology.

[8]  P. Ricciardi-Castagnoli,et al.  Brief Definitive Report Dendritic Cell Survival and Maturation Are Regulated by Different Signaling Pathways , 2022 .

[9]  R. Schlapbach,et al.  TNF‐α and IFN‐γ render microglia sensitive to Fas ligand‐induced apoptosis by induction of Fas expression and down‐regulation of Bcl‐2 and Bcl‐xL , 1998 .

[10]  James M. Roberts,et al.  The murine gene p27Kip1 is haplo-insufficient for tumour suppression , 1998, Nature.

[11]  D. Galloway,et al.  Inhibiting CDK inhibitors: new lessons from DNA tumor viruses. , 1998, Trends in biochemical sciences.

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

[13]  C. Ware,et al.  TNF receptor-deficient mice reveal divergent roles for p55 and p75 in several models of inflammation. , 1998, Journal of immunology.

[14]  K. Matsushima,et al.  Induction of Dendritic Cell Differentiation by Granulocyte-Macrophage Colony-Stimulating Factor, Stem Cell Factor, and Tumor Necrosis Factor α In Vitro From Lineage Phenotypes-Negative c-kit+ Murine Hematopoietic Progenitor Cells , 1997 .

[15]  T. Mak,et al.  Depressed Langerhans cell migration and reduced contact hypersensitivity response in mice lacking TNF receptor p75. , 1997, Journal of immunology.

[16]  B. Stillman,et al.  Inhibition of CDK activity and PCNA-dependent DNA replication by p21 is blocked by interaction with the HPV-16 E7 oncoprotein. , 1997, Genes & development.

[17]  A. Khoruts,et al.  In Vivo Detection of Dendritic Cell Antigen Presentation to CD4+ T Cells , 1997, The Journal of experimental medicine.

[18]  P. Hershberger,et al.  Fas ligand (CD95L) and B7 expression on dendritic cells provide counter-regulatory signals for T cell survival and proliferation. , 1997, Journal of immunology.

[19]  K. Inaba,et al.  Contrasting Effects of TGF‐β1 and TNF‐α on the Development of Dendritic Cells from Progenitors in Mouse Bone Marrow , 1997 .

[20]  Francesca Granucci,et al.  Maturation Stages of Mouse Dendritic Cells in Growth Factor–dependent Long-Term Cultures , 1997, The Journal of experimental medicine.

[21]  P. Ricciardi-Castagnoli,et al.  The role of cytokines in functional regulation and differentiation of dendritic cells. , 1996, Immunobiology.

[22]  J. Banchereau,et al.  CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to GM-CSF+TNF alpha , 1996, The Journal of experimental medicine.

[23]  C Danieli,et al.  Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: downregulation by cytokines and bacterial products , 1995, The Journal of experimental medicine.

[24]  H. Pahl,et al.  A novel signal transduction pathway from the endoplasmic reticulum to the nucleus is mediated by transcription factor NF‐kappa B. , 1995, The EMBO journal.

[25]  P. Morris,et al.  Dendritic cell loss from nonlymphoid tissues after systemic administration of lipopolysaccharide, tumor necrosis factor, and interleukin 1 , 1995, The Journal of experimental medicine.

[26]  D. Goeddel,et al.  Decreased sensitivity to tumour-necrosis factor but normal T-cell development in TNF receptor-2-deficient mice , 1994, Nature.

[27]  F. Sallusto,et al.  Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha , 1994, The Journal of experimental medicine.

[28]  S. Carsons,et al.  Mechanisms of tumor necrosis factor-granulocyte-macrophage colony-stimulating factor-induced dendritic cell development. , 1993, Blood.

[29]  R. Zinkernagel,et al.  Mice lacking the tumour necrosis factor receptor 1 are resistant to IMF-mediated toxicity but highly susceptible to infection by Listeria monocytogenes , 1993, Nature.

[30]  T. Mak,et al.  Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection , 1993, Cell.

[31]  R. Steinman,et al.  Granulocytes, macrophages, and dendritic cells arise from a common major histocompatibility complex class II-negative progenitor in mouse bone marrow. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[32]  J. Banchereau,et al.  GM-CSF and TNF-α cooperate in the generation of dendritic Langerhans cells , 1992, Nature.

[33]  S. Carsons,et al.  TNF in combination with GM‐CSF enhances the differentiation of neonatal cord blood stem cells into dendritic cells and macrophages , 1992, Journal of leukocyte biology.

[34]  G. Schuler,et al.  Tumor necrosis factor alpha maintains the viability of murine epidermal Langerhans cells in culture, but in contrast to granulocyte/macrophage colony-stimulating factor, without inducing their functional maturation , 1990, The Journal of experimental medicine.