| Co-Investigator(Kenkyū-buntansha) |
OKAMURA Haruki Hyogo College of Medicine,Laboratory of Host Defenses, Institute for Advanced Medical Scievces, Professor, 医学部, 教授 (60111043)
NAKANISHI Kenji Hyogo College of Medicine, Department of Immunology and Medical Zoology , Professor, 医学部, 教授 (60172350)
審良 静男 兵庫医科大学, 医学部, 教授 (50192919)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
IL-18, a product of activated macrophages and Kupffer cells, is a potent pleiotropic cytokine. IL-18 induces IFN-γproduction by lymphocytes, such as T cells, and natural killer (NK) cells, particularly in a synergistic manner with IL-12. IL-18 augments NK cell activity through the activation of constitutively express IL-18 receptor on NK cells. In addition, IL-18 upregulates Fas ligand-mediated cytotoxic activity of cloned Th1 cells and NK cells. IL-18 also directly activates CD8ィイD1+ィエD1T cells, which play a central role in viral clearance. Additionally, IL-18 as well as IL-12 is accumulated after infection with microbes or microbe products, allowing us to propose the possibility that IL-18 along with IL-12 participates in microbe clearance and furthermore exogenous IL-18 might enhance host defense. C57BL/6 mice inoculated with the mixture of murine leukemia viruses (MuL Vs) called LP-BM5 MuLV develop an immunodeficiency syndrome which in many ways resembles that seen in humans infected with human immunodecifiency virus type-1 (HIV-1). The function of macrophages and NK cells in HIV infection play a key role developing the diseases. Thus, we examined the function in mouse infected with LP-BM5 MuLV, murine AIDS (MAIDS). We also examined the contribution of IL-18 in developing of MAIDS. The results are following. First, we revealed that serum IL-18 was increased during the course of MAIDS, 〜5μg/ml at 16 weeks after infection . Second, macrophages from MAIDS which infected 8 weeks before produced IL-18 in response to LPS, while those from normal control C57BL/6 mice did not. Third, the expression of B7.2, as an activated cell surface marker on MAIDS macrophages was enhanced. Family, NK activity was augmented 8 weeks after infection with MAIDS.
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