Our group has generated a panel of mice with deficiencies of either TNF or LT separately in T, B cells or macrophages/granulocytes. TNF and especially LT expressed by B cells is critical for development of functional architecture of spleen, but not of lymph nodes. The distinct features in this panel of conditional knock-out is being correlated with the expression pattern of specific genes, including lymphoid tissue chemokines and adhesion molecules. Additionally, we have generated mice with combined p53.TNF/LT deficiency and observed that the deletion of TNF/LT locus results in significant extension of the life span of p53-/- mice.

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC009371-11
Application #
6762185
Study Section
(LMI)
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
2002
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
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
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
Kuprash, D V; Alimzhanov, M B; Tumanov, A V et al. (1999) TNF and lymphotoxin beta cooperate in the maintenance of secondary lymphoid tissue microarchitecture but not in the development of lymph nodes. J Immunol 163:6575-80
Endres, R; Alimzhanov, M B; Plitz, T et al. (1999) Mature follicular dendritic cell networks depend on expression of lymphotoxin beta receptor by radioresistant stromal cells and of lymphotoxin beta and tumor necrosis factor by B cells. J Exp Med 189:159-68
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

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