scholarly journals Trance, a Tumor Necrosis Factor Family Member, Enhances the Longevity and Adjuvant Properties of Dendritic Cells in Vivo

2000 ◽  
Vol 191 (3) ◽  
pp. 495-502 ◽  
Author(s):  
Régis Josien ◽  
Hong-Li Li ◽  
Elizabeth Ingulli ◽  
Supria Sarma ◽  
Brian R.Wong ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Tumor Necrosis Factor ◽  
Lymph Nodes ◽  
Tumor Necrosis ◽  
Ex Vivo ◽  
T Cell Priming ◽  
Draining Lymph Nodes ◽  
Necrosis Factor

Mature dendritic cells (DCs) are powerful antigen presenting cells that have the unique capacity to migrate to the T cell zone of draining lymph nodes after subcutaneous injection. Here we report that treatment of antigen-pulsed mature DCs with tumor necrosis factor (TNF)-related activation-induced cytokine (TRANCE), a TNF family member, before immunization enhances their adjuvant capacity and elicits improved T cell priming in vivo, such that both primary and memory T cell immune responses are enhanced. By enumerating migratory DCs in the draining lymph nodes and by studying their function in stimulating naive T cells, we show that one of the underlying mechanisms for enhanced T cell responses is an increase in the number of ex vivo antigen-pulsed DCs that are found in the T cell areas of lymph nodes. These results suggest that the longevity and abundance of mature DCs at the site of T cell priming influence the strength of the DC-initiated T cell immunity in situ. Our findings have the potential to improve DC-based immunotherapy; i.e., the active immunization of humans with autologous DCs that have been pulsed with clinically significant antigens ex vivo.

scholarly journals Repetitive Injections of Dendritic Cells Matured with Tumor Necrosis Factor α Induce Antigen-specific Protection of Mice from Autoimmunity

2001 ◽  
Vol 195 (1) ◽  
pp. 15-22 ◽  
Author(s):  
Mauritius Menges ◽  
Susanne Rößner ◽  
Constanze Voigtländer ◽  
Heike Schindler ◽  
Nicole A. Kukutsch ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Cell Immunity ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Mature dendritic cells (DCs) are believed to induce T cell immunity, whereas immature DCs induce T cell tolerance. Here we describe that injections of DCs matured with tumor necrosis factor (TNF)-α (TNF/DCs) induce antigen-specific protection from experimental autoimmune encephalomyelitis (EAE) in mice. Maturation by TNF-α induced high levels of major histocompatibility complex class II and costimulatory molecules on DCs, but they remained weak producers of proinflammatory cytokines. One injection of such TNF/DCs pulsed with auto-antigenic peptide ameliorated the disease score of EAE. This could not be observed with immature DCs or DCs matured with lipopolysaccharide (LPS) plus anti-CD40. Three consecutive injections of peptide-pulsed TNF/DCs derived from wild-type led to the induction of peptide-specific predominantly interleukin (IL)-10–producing CD4+ T cells and complete protection from EAE. Blocking of IL-10 in vivo could only partially restore the susceptibility to EAE, suggesting an important but not exclusive role of IL-10 for EAE prevention. Notably, the protection was peptide specific, as TNF/DCs pulsed with unrelated peptide could not prevent EAE. In conclusion, this study describes that stimulation by TNF-α results in incompletely matured DCs (semi-mature DCs) which induce peptide-specific IL-10–producing T cells in vivo and prevent EAE.

scholarly journals Mast cell–derived particles deliver peripheral signals to remote lymph nodes

2009 ◽  
Vol 206 (11) ◽  
pp. 2455-2467 ◽  
Author(s):  
Christian A. Kunder ◽  
Ashley L. St. John ◽  
Guojie Li ◽  
Kam W. Leong ◽  
Brent Berwin ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Mast Cell ◽  
Mast Cells ◽  
Tumor Necrosis Factor ◽  
Lymph Nodes ◽  
Tumor Necrosis ◽  
Lymphatic Vessels ◽  
Lymphoid Tissues ◽  
Draining Lymph Nodes ◽  
Necrosis Factor

During infection, signals from the periphery are known to reach draining lymph nodes (DLNs), but how these molecules, such as inflammatory cytokines, traverse the significant distances involved without dilution or degradation remains unclear. We show that peripheral mast cells, upon activation, release stable submicrometer heparin-based particles containing tumor necrosis factor and other proteins. These complexes enter lymphatic vessels and rapidly traffic to the DLNs. This physiological drug delivery system facilitates communication between peripheral sites of inflammation and remote secondary lymphoid tissues.

scholarly journals Prostaglandin E2 and Tumor Necrosis Factor α Cooperate to Activate Human Dendritic Cells: Synergistic Activation of Interleukin 12 Production

1997 ◽  
Vol 186 (9) ◽  
pp. 1603-1608 ◽  
Author(s):  
Claudia Rieser ◽  
Günther Böck ◽  
Helmut Klocker ◽  
Georg Bartsch ◽  
Martin Thurnher
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Tumor Necrosis Factor ◽  
Prostaglandin E2 ◽  
Tumor Necrosis ◽  
Interleukin 12 ◽  
Dependent Manner ◽  
Tnf Α ◽  
Human Dendritic Cells ◽  
Necrosis Factor

Interleukin (IL)-12 is a proinflammatory cytokine that contributes to innate resistance and to the development of antigen-specific T cell responses. Among other effects, prostaglandin E2 (PGE2) inhibits the production of IL-12 by macrophages activated with lipopolysaccharide (LPS). Here we investigated the effects of PGE2 on human dendritic cells (DCs) which develop in the presence of GM-CSF and IL-4. We demonstrate that in the absence of LPS, PGE2 dose dependently stimulated the production of IL-12 by DCs. Although PGE2 alone stimulated the production of low amounts of IL-12 only, it synergized with tumor necrosis factor (TNF)-α to induce high levels of IL-12 production by DCs. Addition of TNF-α in the absence of PGE2 had no effect on IL-12 production. Conversely, in the presence of LPS, PGE2 inhibited IL-12 production by DCs in a dose-dependent manner. The combination of PGE2 and TNF-α efficiently silenced mannose receptor–mediated endocytosis in DCs and readily induced neo-expression of the CD83 antigen. In addition, the expression of various surface antigens such as major histocompatibility complex class I and II, adhesion, as well as costimulatory molecules was upregulated by this treatment. The effects of PGE2 on IL-12 synthesis and CD83 expression could be mimicked by dibutyryl-cAMP and forskolin, indicating that they were due to the intracellular elevation of cAMP levels. DC treated with PGE2 and TNF-α were most potent in stimulating allogeneic T cell proliferation. Our data demonstrate that PGE2 contributes to the maturation of human DCs and that PGE2 can be a potent enhancer of IL-12 production by human DCs.

Regulatory T Cells Expressing Tumor Necrosis Factor Receptor Type 2 Play a Major Role in CD4+ T-Cell Impairment During Sepsis

2020 ◽  
Vol 222 (7) ◽  
pp. 1222-1234 ◽  
Author(s):  
Benjamin J Gaborit ◽  
Antoine Roquilly ◽  
Cédric Louvet ◽  
Abderrahmane Sadek ◽  
Benoit Tessoulin ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Necrosis Factor ◽  
Regulatory T Cells ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Cd4 T Cell ◽  
Treg Subset ◽  
Necrosis Factor

Abstract Sepsis causes inflammation-induced immunosuppression with lymphopenia and alterations of CD4+ T-cell functions that renders the host prone to secondary infections. Whether and how regulatory T cells (Treg) are involved in this postseptic immunosuppression is unknown. We observed in vivo that early activation of Treg during Staphylococcus aureus sepsis induces CD4+ T-cell impairment and increases susceptibility to secondary pneumonia. The tumor necrosis factor receptor 2 positive (TNFR2pos) Treg subset endorsed the majority of effector immunosuppressive functions, and TNRF2 was particularly associated with activation of genes involved in cell cycle and replication in Treg, probably explaining their maintenance. Blocking or deleting TNFR2 during sepsis decreased the susceptibility to secondary infection. In humans, our data paralleled those in mice; the expression of CTLA-4 was dramatically increased in TNFR2pos Treg after culture in vitro with S. aureus. Our findings describe in vivo mechanisms underlying sepsis-induced immunosuppression and identify TNFR2pos Treg as targets for therapeutic intervention.

Effects of recombinant tumor necrosis factor (rHuTNFα)on human neutrophils and monocytes: In vitro, ex vivo and in vivo

2009 ◽  
Vol 43 (4) ◽  
pp. 286-296 ◽  
Author(s):  
E. Schell-Frederick ◽  
T. Tepass ◽  
G. Lorscheidt ◽  
M. Pfreundschuh ◽  
M. Schaadt ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Ex Vivo ◽  
Human Neutrophils ◽  
Recombinant Tumor Necrosis Factor ◽  
Necrosis Factor

scholarly journals Tumor Necrosis Factor–dependent Segmental Control of MIG Expression by High Endothelial Venules in Inflamed Lymph Nodes Regulates Monocyte Recruitment

2001 ◽  
Vol 194 (9) ◽  
pp. 1375-1384 ◽  
Author(s):  
Mary J. Janatpour ◽  
Susan Hudak ◽  
Manjiri Sathe ◽  
Jonathon D. Sedgwick ◽  
Leslie M. McEvoy
Keyword(s):  
Lymph Node ◽  
Tumor Necrosis Factor ◽  
Lymph Nodes ◽  
Tumor Necrosis ◽  
Ex Vivo ◽  
Small Subset ◽  
Blood Monocytes ◽  
High Endothelial Venules ◽  
Monocyte Recruitment ◽  
Necrosis Factor

Monocytes recruited from the blood are key contributors to the nature of an immune response. While monocyte recruitment in a subset of immunopathologies has been well studied and largely attributed to the chemokine monocyte chemoattractant protein (MCP)-1, mechanisms mediating such recruitment to other sites of inflammation remain elusive. Here, we showed that localized inflammation resulted in an increased binding of monocytes to perifollicular high endothelial venules (HEVs) of lymph nodes draining a local inflammatory site. Quantitative PCR analyses revealed the upregulation of many chemokines in the inflamed lymph node, including MCP-1 and MIG. HEVs did not express detectable levels of MCP-1; however, a subset of HEVs in inflamed lymph nodes in wild-type (but not tumor necrosis factor [TNF] null mice) expressed MIG and this subset of HEVs preferentially supported monocyte binding. Expression of CXCR3, the receptor for MIG, was detected on a small subset of peripheral blood monocytes and on a significant percentage of recruited monocytes. Most importantly, in both ex vivo and in vivo assays, neutralizing anti-MIG antibodies blocked monocyte binding to inflamed lymph node HEVs. Together, these results suggest that the lymph node microenvironment can dictate the nature of molecules expressed on HEV subsets in a TNF-dependent fashion and that inflammation-induced MIG expression by HEVs can mediate monocyte recruitment.

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