scholarly journals Defective Peyer's patch organogenesis in mice lacking the 55-kD receptor for tumor necrosis factor.

1996 ◽  
Vol 184 (1) ◽  
pp. 259-264 ◽  
Author(s):  
B Neumann ◽  
A Luz ◽  
K Pfeffer ◽  
B Holzmann
Keyword(s):  
Tumor Necrosis Factor ◽  
Lymph Nodes ◽  
Tumor Necrosis ◽  
Peyer's Patches ◽  
Mutant Mice ◽  
Peyer’S Patches ◽  
White Pulp ◽  
Genetic Ablation ◽  
Deficient Mice ◽  
Necrosis Factor

Lymphotoxin alpha (LT-alpha) may form secreted homotrimers binding to p55 and p75 tumor necrosis factor (TNF) receptors or cell surface-bound heterotrimers with LT-beta that interact with the LT-beta receptor. Genetic ablation of LT-alpha revealed that mutant mice have no detectable lymph nodes or Peyer's patches and that the organization of the splenic white pulp in T and B cell areas is disturbed. In this report we describe a novel function for the p55 TNF receptor during ontogeny and demonstrate that mice deficient for p55 completely lack organized Peyer's patches. In contrast, lymph nodes and spleen are present in p55-deficient mice and lymphocytes segregate normally into B and T cell areas in these organs. Lamina propria and intraepithelial lymphocytes of the small intestine were detected in normal number and distribution in p55 mutant mice. Lymphocytes and endothelial cells from p55-deficient mice express normal levels of adhesion molecules considered important for lymphocyte migration to mucosal organs; this indicates that the lack of Peyer's patches does not result from a defect in lymphocyte homing. In summary, the p55 receptor for TNF selectively mediates organogenesis of Peyer's patches throughout ontogeny, suggesting that the effects of LT-alpha on the development of lymphoid organs may be mediated by distinct receptors, each functioning in an organ-specific context.

Novel tumor necrosis factor-knockout mice that lack Peyer's patches

2005 ◽  
Vol 35 (5) ◽  
pp. 1592-1600 ◽  
Author(s):  
Dmitry?V. Kuprash ◽  
Alexei V. Tumanov ◽  
Dmitry?J. Liepinsh ◽  
Ekaterina?P. Koroleva ◽  
Marina?S. Drutskaya ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Knockout Mice ◽  
Tumor Necrosis ◽  
Peyer's Patches ◽  
Peyer’S Patches ◽  
Necrosis Factor

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.

Immunodeficiency of Tumor Necrosis Factor and Lymphotoxin-α Double-Deficient Mice

1998 ◽  
pp. 103-118 ◽  
Author(s):  
Hans-Pietro Eugster ◽  
Matthias Müller ◽  
Michel Le Hir ◽  
Bernhard Ryffel
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Lymphotoxin Α ◽  
Deficient Mice ◽  
Necrosis Factor

scholarly journals Induction of Interleukin-4 (IL-4) by Legionella pneumophila Infection in BALB/c Mice and Regulation of Tumor Necrosis Factor Alpha, IL-6, and IL-1β

2000 ◽  
Vol 68 (9) ◽  
pp. 5234-5240 ◽  
Author(s):  
Catherine Newton ◽  
Shannon McHugh ◽  
Ray Widen ◽  
Noriya Nakachi ◽  
Thomas Klein ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Legionella Pneumophila ◽  
Tumor Necrosis ◽  
Ex Vivo ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Deficient Mice ◽  
Necrosis Factor

ABSTRACT Infection of BALB/c mice with a sublethal concentration ofLegionella pneumophila causes an acute disease that is resolved by innate immune responses. The infection also initiates the development of adaptive Th1 responses that protect the mice from challenge infections. To study the early responses, cytokines induced during the first 24 h after infection were examined. In the serum, interleukin-12 (IL-12) was detectable by 3 h and peaked at 10 h, while gamma interferon was discernible by 5 h and peaked at 8 h. Similar patterns were observed in ex vivo cultures of splenocytes. A transient IL-4 response was also detected by 3 h postinfection in ex vivo cultures. BALB/c IL-4-deficient mice were more susceptible to L. pneumophila infection than were wild-type mice. The infection induced higher serum levels of acute-phase cytokines (tumor necrosis factor alpha [TNF-α], IL-1β, and IL-6), and reducing TNF-α levels with antibodies protected the mice from death. Moreover, the addition of IL-4 to L. pneumophila-infected macrophage cultures suppressed the production of these cytokines. Thus, the lack of IL-4 in the deficient mice resulted in unchecked TNF-α production, which appeared to cause the mortality. Monocyte chemoattractant protein-1 (MCP-1), a chemokine that is induced by IL-4 during Listeria monocytogenesinfection, was detected at between 2 and 30 h after infection. However, MCP-1 did not appear to be induced by IL-4 or to be required for the TNF-α regulation by IL-4. The data suggest that the early increase in IL-4 serves to regulate the mobilization of acute phase cytokines and thus controls the potential harmful effects of these cytokines.

scholarly journals An Essential Role for Tumor Necrosis Factor in Natural Killer Cell–mediated Tumor Rejection in the Peritoneum

1998 ◽  
Vol 188 (9) ◽  
pp. 1611-1619 ◽  
Author(s):  
Mark J. Smyth ◽  
Janice M. Kelly ◽  
Alan G. Baxter ◽  
Heinrich Körner ◽  
Jonathon D. Sedgwick
Keyword(s):  
Tumor Necrosis Factor ◽  
Nk Cells ◽  
Natural Killer ◽  
Mhc Class I ◽  
Tumor Necrosis ◽  
Nk Cell ◽  
Tumor Rejection ◽  
Class I ◽  
Deficient Mice ◽  
Necrosis Factor

Natural killer (NK) cells are thought to provide the first line of defence against tumors, particularly major histocompatibility complex (MHC) class I− variants. We have confirmed in C57BL/6 (B6) mice lacking perforin that peritoneal growth of MHC class I− RMA-S tumor cells in unprimed mice is controlled by perforin-dependent cytotoxicity mediated by CD3− NK1.1+ cells. Furthermore, we demonstrate that B6 mice lacking tumor necrosis factor (TNF) are also significantly defective in their rejection of RMA-S, despite the fact that RMA-S is insensitive to TNF in vitro and that spleen NK cells from B6 and TNF-deficient mice are equally lytic towards RMA-S. NK cell recruitment into the peritoneum was abrogated in TNF-deficient mice challenged with RMA-S or RM-1, a B6 MHC class I− prostate carcinoma, compared with B6 or perforin-deficient mice. The reduced NK cell migration to the peritoneum of TNF-deficient mice correlated with the defective NK cell response to tumor in these mice. By contrast, a lack of TNF did not affect peptide-specific cytotoxic T lymphocyte–mediated rejection of tumor from the peritoneum of preimmunized mice. Overall, these data show that NK cells delivering perforin are the major effectors of class I− tumor rejection in the peritoneum, and that TNF is specifically critical for their recruitment to the peritoneum.

scholarly journals Lymphotoxin α/β and Tumor Necrosis Factor Are Required for Stromal Cell Expression of Homing Chemokines in B and T Cell Areas of the Spleen

1999 ◽  
Vol 189 (2) ◽  
pp. 403-412 ◽  
Author(s):  
Vu N. Ngo ◽  
Heinrich Korner ◽  
Michael D. Gunn ◽  
Kerstin N. Schmidt ◽  
D. Sean Riminton ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Necrosis Factor ◽  
Stromal Cells ◽  
Tumor Necrosis ◽  
B Lymphocyte ◽  
Spleen Deficiency ◽  
Barr Virus ◽  
Adult Mice ◽  
Deficient Mice ◽  
Necrosis Factor

Mice deficient in the cytokines tumor necrosis factor (TNF) or lymphotoxin (LT) α/β lack polarized B cell follicles in the spleen. Deficiency in CXC chemokine receptor 5 (CXCR5), a receptor for B lymphocyte chemoattractant (BLC), also causes loss of splenic follicles. Here we report that BLC expression by follicular stromal cells is defective in TNF-, TNF receptor 1 (TNFR1)-, LTα- and LTβ-deficient mice. Treatment of adult mice with antagonists of LTα1β2 also leads to decreased BLC expression. These findings indicate that LTα1β2 and TNF have a role upstream of BLC/CXCR5 in the process of follicle formation. In addition to disrupted follicles, LT-deficient animals have disorganized T zones. Expression of the T cell attractant, secondary lymphoid tissue chemokine (SLC), by T zone stromal cells is found to be markedly depressed in LTα-, and LTβ-deficient mice. Expression of the SLC-related chemokine, Epstein Barr virus–induced molecule 1 ligand chemokine (ELC), is also reduced. Exploring the basis for the reduced SLC expression led to identification of further disruptions in T zone stromal cells. Together these findings indicate that LTα1β2 and TNF are required for the development and function of B and T zone stromal cells that make chemokines necessary for lymphocyte compartmentalization in the spleen.

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