CD137-Deficient Mice Have Reduced NK/NKT Cell Numbers and Function, Are Resistant to Lipopolysaccharide-Induced Shock Syndromes, and Have Lower IL-4 Responses

• Published in: The Journal of immunology (1950) Vol. 173; no. 6; pp. 4218 - 4229
• Main Authors: Vinay, Dass S, Choi, Beom K, Bae, Jun S, Kim, Won Y, Gebhardt, Bryan M, Kwon, Byoung S
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.09.2004
• Subjects: 4-1BB Ligand; Animals; Antibodies, Blocking - pharmacology; Antigens, CD; Cell Line, Tumor; Cells, Cultured; Chemical and Drug Induced Liver Injury - genetics; Chemical and Drug Induced Liver Injury - immunology; Chemical and Drug Induced Liver Injury - pathology; Cytotoxicity, Immunologic - genetics; Immunity, Innate - genetics; Interferon-gamma - antagonists & inhibitors; Interferon-gamma - biosynthesis; Interferon-gamma - genetics; Interleukin-4 - antagonists & inhibitors; Interleukin-4 - metabolism; Interleukin-4 - physiology; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Killer Cells, Natural - pathology; Ligands; Lipopolysaccharides - toxicity; Lymphocyte Count; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Receptors, Nerve Growth Factor - antagonists & inhibitors; Receptors, Nerve Growth Factor - deficiency; Receptors, Nerve Growth Factor - genetics; Receptors, Nerve Growth Factor - physiology; Receptors, Tumor Necrosis Factor - antagonists & inhibitors; Receptors, Tumor Necrosis Factor - deficiency; Receptors, Tumor Necrosis Factor - genetics; Receptors, Tumor Necrosis Factor - physiology; Shock, Septic - genetics; Shock, Septic - immunology; Shock, Septic - pathology; Shock, Septic - prevention & control; Signal Transduction - genetics; Signal Transduction - immunology; Syndrome; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocyte Subsets - pathology; Th2 Cells - immunology; Th2 Cells - metabolism; Tumor Necrosis Factor Receptor Superfamily, Member 9; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - immunology; Tumor Necrosis Factor-alpha - physiology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.173.6.4218

CD137, a member of the TNF superfamily, is involved in T cell and NK cell activation and cytokine production. To establish its in vivo role in systems dependent on NK and NKT cells, we studied the response of CD137-/- mice to LPS-induced shock, tumor killing, and their IL-4-controlled Th2 responses. In both high and low dose shock models, all the CD137-deficient mice, but none of the wild-type BALB/c mice, survived. After injection of LPS/2-amino-2-deoxy-D-galactose (D-gal), CD137-/- mice had reduced serum cytokine levels and substantially impaired liver IFN-gamma and TNF-alpha mRNA levels. Phenotypic analysis of mononuclear cells revealed fewer NK and NKT cells in the CD137-/- mice. The knockout mice did not generate a rapid IL-4 response after systemic T cell activation, or effective Ag-specific Th2 responses. In addition, both in vitro and in vivo NK-specific cytolytic activities were reduced. These findings suggest that CD137-directed NK/NKT cells play an important role in the inflammatory response leading to the production of proinflammatory cytokines, LPS-induced septic shock, and tumor killing, as well as IL-4-dependent Th2 responses.