We further characterized the neo-free TNF KO mice completely lacking the Peyer's patches (in collaboration with J. Berzovsky lab at NCI and W. Murphy at University of Nevada). We generated and characterized novel mice """"""""humanized"""""""" for the TNF/LT locus. In one founder a modest overexpression of TNF/LT resulted in TNFRp55-mediated thymic athrophy. Effects of inducible ablation of either TNF or LT signalling in both pharmacological and genetic settings are being evaluated with specific focus on the integrity of lymphoid organ structure. Additonally, in collaboration with R. Zinkernagel lab in Zurich we addressed the link between the integrity of peripheral lymphoid tissues and anti-viral immunity. Finally, in collaboration with J. Keller and J. Ryan (Virginia Commonwealth University) we evaluated hematopoiesis in TNF, LT and TNF/LT knockout mice.

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC009371-14
Application #
7291730
Study Section
(BRL)
Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
2005
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Kuprash, Dmitry V; Tumanov, Alexei V; Liepinsh, Dmitry J et al. (2005) Novel tumor necrosis factor-knockout mice that lack Peyer's patches. Eur J Immunol 35:1592-600
Grivennikov, Sergei I; Tumanov, Alexei V; Liepinsh, Dmitry J et al. (2005) Distinct and nonredundant in vivo functions of TNF produced by t cells and macrophages/neutrophils: protective and deleterious effects. Immunity 22:93-104
Shakhov, Alexander N; Rybtsov, Stanislav; Tumanov, Alexei V et al. (2004) SMUCKLER/TIM4 is a distinct member of TIM family expressed by stromal cells of secondary lymphoid tissues and associated with lymphotoxin signaling. Eur J Immunol 34:494-503
Tumanov, Alexei V; Kuprash, Dmitry V; Mach, Julie A et al. (2004) Lymphotoxin and TNF produced by B cells are dispensable for maintenance of the follicle-associated epithelium but are required for development of lymphoid follicles in the Peyer's patches. J Immunol 173:86-91
Tumanov, Alexei V; Grivennikov, Sergei I; Shakhov, Alexander N et al. (2003) Dissecting the role of lymphotoxin in lymphoid organs by conditional targeting. Immunol Rev 195:106-16
Abe, Koichiro; Yarovinsky, Felix O; Murakami, Takaya et al. (2003) Distinct contributions of TNF and LT cytokines to the development of dendritic cells in vitro and their recruitment in vivo. Blood 101:1477-83
Tumanov, Alexei V; Kuprash, Dmitry V; Nedospasov, Sergei A (2003) The role of lymphotoxin in development and maintenance of secondary lymphoid tissues. Cytokine Growth Factor Rev 14:275-88
Baer, M; Nedospasov, S; Johnson, P F (1999) Attenuation of tumor necrosis factor alpha gene transcription in macrophages by an autocrine factor. Cold Spring Harb Symp Quant Biol 64:437-44
Kuprash, D V; Udalova, I A; Turetskaya, R L et al. (1999) Similarities and differences between human and murine TNF promoters in their response to lipopolysaccharide. J Immunol 162:4045-52
Ito, D; Back, T C; Shakhov, A N et al. (1999) Mice with a targeted mutation in lymphotoxin-alpha exhibit enhanced tumor growth and metastasis: impaired NK cell development and recruitment. J Immunol 163:2809-15

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