scholarly journals Long-term inhibition of tumor growth by tumor necrosis factor in the absence of cachexia or T-cell immunity.

1991 ◽  
Vol 88 (9) ◽  
pp. 3535-3539 ◽  
Author(s):  
M. N. Teng ◽  
B. H. Park ◽  
H. K. Koeppen ◽  
K. J. Tracey ◽  
B. M. Fendly ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Necrosis Factor ◽  
Tumor Growth ◽  
Tumor Necrosis ◽  
T Cell Immunity ◽  
Cell Immunity ◽  
Inhibition Of Tumor Growth ◽  
Necrosis Factor

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 Targeting Mycobacterium tuberculosis Tumor Necrosis Factor Alpha-Downregulating Genes for the Development of Antituberculous Vaccines

mBio ◽  
2016 ◽  
Vol 7 (3) ◽  
Author(s):  
Aaron Olsen ◽  
Yong Chen ◽  
Qingzhou Ji ◽  
Guofeng Zhu ◽  
Aruna Dharshan De Silva ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Necrosis Factor ◽  
Host Cell ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Cell Responses ◽  
Cell Immunity ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Tumor necrosis factor alpha (TNF) plays a critical role in the control of Mycobacterium tuberculosis , in part by augmenting T cell responses through promoting macrophage phagolysosomal fusion (thereby optimizing CD4 + T cell immunity by enhancing antigen presentation) and apoptosis (a process that can lead to cross-priming of CD8 + T cells). M. tuberculosis can evade antituberculosis (anti-TB) immunity by inhibiting host cell TNF production via expression of specific mycobacterial components. We hypothesized that M. tuberculosis mutants with an increased capacity to induce host cell TNF production (TNF-enhancing mutants) and thus with enhanced immunogenicity can be useful for vaccine development. To identify mycobacterial genes that regulate host cell TNF production, we used a TNF reporter macrophage clone to screen an H37Rv M. tuberculosis cosmid library constructed in M. smegmatis . The screen has identified a set of TNF-downregulating mycobacterial genes that, when deleted in H37Rv, generate TNF-enhancing mutants. Analysis of mutants disrupted for a subset of TNF-downregulating genes, annotated to code for triacylglycerol synthases and fatty acyl-coenzyme A (acyl-CoA) synthetase, enzymes that concern lipid biosynthesis and metabolism, has revealed that these strains can promote macrophage phagolysosomal fusion and apoptosis better than wild-type (WT) bacilli. Immunization of mice with the TNF-enhancing M. tuberculosis mutants elicits CD4 + and CD8 + T cell responses that are superior to those engendered by WT H37Rv. The results suggest that TNF-upregulating M. tuberculosis genes can be targeted to enhance the immunogenicity of mycobacterial strains that can serve as the substrates for the development of novel anti-TB vaccines. IMPORTANCE One way to control tuberculosis (TB), which remains a major global public health burden, is by immunization with an effective vaccine. The efficacy of Mycobacterium bovis BCG, the only currently approved TB vaccine, is inconsistent. Tumor necrosis factor alpha (TNF) is a cytokine that plays an important role in controlling TB. M. tuberculosis , the causative agent of TB, can counter this TNF-based defense by decreasing host cell TNF production. This study identified M. tuberculosis genes that can mediate inhibition of TNF production by macrophage (an immune cell critical to the control of TB). We have knocked out a number of these genes to generate M. tuberculosis mutants that can enhance macrophage TNF production. Immunization with these mutants in mice triggered a T cell response stronger than that elicited by the parental bacillus. Since T cell immunity is pivotal in controlling M. tuberculosis , the TNF-enhancing mutants can be used to develop novel TB vaccines.

Porcine hematopoiesis on primate stroma in long-term cultures: enhanced growth with neutralizing tumor necrosis factor-?? and tumor growth factor-?? antibodies

2002 ◽  
Vol 73 (5) ◽  
pp. 723-731 ◽  
Author(s):  
Maria A. Giovino ◽  
Julian D. Down ◽  
John D. Jackson ◽  
Megan Sykes ◽  
Rodney L. Monroy ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tumor Necrosis Factor ◽  
Tumor Growth ◽  
Tumor Necrosis ◽  
Tumor Growth Factor ◽  
Necrosis Factor

scholarly journals Importance of T Cells, Gamma Interferon, and Tumor Necrosis Factor in Immune Control of the Rapid Grower Mycobacterium abscessus in C57BL/6 Mice

2007 ◽  
Vol 75 (12) ◽  
pp. 5898-5907 ◽  
Author(s):  
Martin Rottman ◽  
Emilie Catherinot ◽  
Patrick Hochedez ◽  
Jean-François Emile ◽  
Jean-Laurent Casanova ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Necrosis Factor ◽  
B Cell ◽  
Tumor Necrosis ◽  
Mycobacterium Abscessus ◽  
Gamma Interferon ◽  
Immune Control ◽  
Cell Immunity ◽  
Ifn Γ ◽  
Necrosis Factor

ABSTRACT Mycobacterium abscessus is an emerging rapidly growing mycobacterium that causes tuberculous-like lesions in humans. We studied the immune control of this organism in C57BL/6 mice challenged intravenously with 107 CFU. Bacteria were eliminated from both the spleen and the liver within 90 days, and liver histology showed organized granulomatous lesions. A T- and B-cell requirement was investigated by challenging Rag2 − / −, Cd3ε− / −, and μMT − / − mice. Rag2 − / − and Cd3ε− / − mice were significantly impaired in the ability to clear M. abscessus from the liver and spleen, and μMT − / − mice were significantly impaired in the ability to clear M. abscessus from the liver, suggesting that infection control was primarily T cell dependent in the spleen and both T and B cell dependent in the liver. The liver granulomatous response was similar to that of wild-type controls in μMT − / − mice but completely absent in Cd3ε− / − and Rag2 − / − mice. We studied the involvement of gamma interferon (IFN-γ) and tumor necrosis factor (TNF) by challenging C57BL/6 mice deficient in the IFN-γ receptor (Ifngr1 − / −) and in TNF (Tnf − / −). Ifngr1 − / − mice were significantly impaired in M. abscessus control both in the spleen and in the liver, and granulomas were profoundly altered. The effect was even more substantial in Tnf − / − mice; they failed to control M. abscessus infection in the liver and died within 20 to 25 days after infection with many hepatic inflammatory foci and major lesions of ischemic necrosis in the liver and kidney. These features were not observed with the closely related species M. chelonae. T-cell immunity, IFN-γ, and TNF are central factors for the control of M. abscessus in C57BL/6 mice, as they are for the control of pathogenic slowly growing mycobacteria.

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