1999 Fiscal Year Final Research Report Summary
Analysis for the pathogenesis of concomitant infection in AIDS and murine AIDS
| Project/Area Number |
10045068
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | Nagoya University |
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Principal Investigator |
YOSHIKAI Yasunobu Nagoya University, School of Medicine, Professor, 医学部, 教授 (90158402)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIMURA Hitoshi School of Medicine, Research Associate, 医学部, 助手 (00283440)
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| Project Period (FY) |
1998 – 1999
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| Keywords | MAIDS / Mycobacteria / host defense / IL-15 / transgenic mice / memory CD8 T cells / NK cells / γδT cells |
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| Research Abstract |
LP-BM5 murine leukemia virus (MuLV) injection is a causative of murine AIDS (MAIDS), characterized by a variety of functional abnormalities of immunocompetent cells and susceptibility to various infectious with Mycobacterium avium or M. bovis BCG as assessed by survival rate and bacterial counts. The expression of IL-15 in the peritoneal macrophages was severely impaired in MAIDS mice following infection with M. bovis BCG. NK cells were increased in the peritoneal cavity of normal mice at earl stage after BCG infection, whereas such increases were not evident in MAIDS mice. Serum IFN-γ level was also depressed in MAIDS mice following BCG infection. The production IFN-γ by T cells from the MAIDS mice infected with M. bovis BCG was significantly lower in response to PPD than that of normal mice infected with M. bovis BCG. These results suggested that depressed IL-15 production in MAIDS mice might be involved in susceptibility against M. bovis BCG.
To elucidate the protective roles of IL-15 in the progression of MAIDS, we constructed transgenic mice using IL-15 cDNA under the control of an MHC class I promoter. The IL-15 Tg mice constitutionally produced a significant level of IL-15 protein and had markedly increased numbers of memory type (CD44ィイD1highィエD1 Ly6CィイD1+ィエD1) of CD8ィイD1+ィエD1T cells in the LN. These mice showed resistance to LP-BM5 infection accompanied by increases in NK cells and memory CD8ィイD1+ィエD1 T cells and enhanced IFN-γ production. Thus, these findings suggest that IL-15 production is partly responsible for MAIDS progression and that IL-15 may be protective for MAIDS and presumably AIDS progression.
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[Publications] Kimura, Y., Yamada, K., Sakai, T., Mishima, K., Nishimura, H., Matsumoto Y., Singh, M., and Yoshikai, Y.: "The regulatory role of heat shock protein 70-reactive Cd4ィイD1+ィエD1 T cells during rat listeriosis"Int. Immunol.. 10. 117-130 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Sakai, T. Kusugami, K., Nishimura, H., Nishimura, H., Ando, T., Yamaguchi, T., Ohsuga, M., Ina, K., Enomoto, A., Kimura, Y. and Yoshikai, Y.: "Interleukin 15 Activity in the rectal mucosa of inflammatory bowel disease"Gastroenterology. 114. 1237-1243 (1998)
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[Publications] Takano,M., Arai,T., Mokuno,Y., Nishimura,H., Nimura,Y., and Yoshikai., Y.: "Dibutyryl cyclic adenosine monophosphate protects mice against tumor necrosis factor-α-induced hepatocyte apoptosis accompanied by increased heat shock protein 70 expression"Cell Stress Chaperones. 3. 109-117 (1998)
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[Publications] Murosaki,S., Yamamoto,Y., Ito,K., Inokuchi,T., Kusaka,H., Ikeda,H., and Yoshikai,Y.: "Heat-killed Lactobacillius plantarum L-137 suppresses naturally fed antigen-specific IgE production by stimulation of IL-12 production in mice"J. Allergy Clin. Immunol. 102. 57-64 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Takano,M., Nishimura,H., Kimura,Y., Washizu,J., Nimura,Y., and Yoshikai,Y.: "Prostaglandin E2 protects against liver injury after Escherichia coli infection but hampers the resolution of the infection in mice"J. Immunol.. 161. 3019-3025 (1998)
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[Publications] Hirose,K., Suzuki.,H., Nishimura,H., Mitani., A., Washizu,J., Matsuguchi,T. and Yoshikai,Y.: "Interleukin-15 might be responsible early activation of intertinal intraepithelial lymphocytes after oral infection with Listeria monocytogenes in rats"Infect. Immun.. 66. 5677-5683 (1998)
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[Publications] Kimura,K., Nishimura,H., Hirose,K., Matsuguchi,T., Nimura,Y. and Yoshikai,Y.: "Immunogene therapy formurine fibrosarcoma using IL-15 gene with high translation efficiency"Eur.J. Immunol.. 29. 1532-1542 (1999)
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[Publications] Yamada,K.,Kimura,Y.,Nishimura,H.,Namii,Y.,Murase,M. and Yoshikai,Y.: "Characterization of CD4ィイD1+ィエD1 CD8ααィイD1+ィエD1 and CD4ィイD1-ィエD1 CD8ααィイD1+ィエD1 intestinal intraepithelial lymphocytes in rats"Int. Immunol.. 11. 21-28 (1999)
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[Publications] Nishimura,H., Washizu,J., Naiki,Y., Fukui,Y., Sasazuki, T. and Yoshikai,Y.: "MHC class II-dependent NK1.1ィイD1+ィエD1γδ T cells are induced in mice by Salmonella infection"J. Immunol.. 162. 1573-1581 (1999)
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[Publications] Ishigami,M., Nishimura,H., Naiki,Y., Yoshioka,Y., Kawano,T., Tanaka,Y., Taniguchi,M., Kakumu,S., and Yoshikai,Y.: "The roles of intrahepatic Vα14ィイD1+ィエD1 NK1.1ィイD1+ィエD1 T cells for liver injury induced by Salmonella infection"Hepatology. 29. 1799-1808 (1999)
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[Publications] Murosaki,S., Muroyama,K., Yamamoto,Y., Kusaka,H., Liu,Tiei., and Yoshikai,Y.: "Immunopotentiating activityof nigerooligosaccharides for T helper 1-like immune response in mice"Biosci. Biotechnol. Biochem.. 63. 373-378 (1999)
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[Publications] Naiki,Y., Nishimura,H., Kawano,T., Tanaka,Y., Itohara,S., Taniguchi,M., Yoshikai,Y.: "Regulatory role of peritoneal NK1.1+αβ T cells in IL-12 production during Salmonella infection"J. Immunol.. 163. 2057-2063 (1999)
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[Publications] Tanaka,S., Kimura,Y., Mitani,A., Yamamoto,G., Nishimura,H., Spaller,R., Singh,M.,Noguchi,T., Yoshikai.Y.: "Activation of T cells recognizing an epitope of heat shock protein (HSP) 70 can protect against rat adjuvant arthritis"J. Immunol.. 163. 5560-5565 (1999)
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[Publications] Mokuno,Y., Takano,M., Matsuguchi,T., Nishimura, H., Washizu,J., Naiki,Y., Kimura, Y., and Yoshikai, Y.: "Prostaglandin EィイD21ィエD2 protects against liver injury induced by Escherichia coliinfection via a dominant Th2-like response of liver T cells in mice"Hepatology. 30. 1464-1472 (1999)
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[Publications] Nishimura, H., Yajima, T., Naiki, Y., Tsunobuchi, H., Umemura, M., Itano, K.,Matsuguchi, T., Suzuki, M., Ohashi, P, M., and Yoshikai.Y.: "Differencial roles of IL-15 mRNA isoforms generated by alternative splicing in immune responses in vivo"J. Exp. Med.. 191. 157-170 (2000)
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[Publications] Mokuno,Y., Matsuguchi,T., Takano, M., Nishimura, H., Washizu,J., Ogawa,T., Nimura,Y. and Yoshikai Y.: "γδ T cells bearing invariant Vγ6/Vδ1 may respond to lipid A via Toll-like receptor 2"J. Immunol.. in press. (2000)
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[Publications] Kimura,K., Nishimura, H., Matsuzaki,T., Yokokura, T., Nimura,Y and Yoshikai, Y.: "Synegistic effect of IL-15 and IL-12 on anti-tumor activity in a murine malignant pleurisy model"Cancer. Immunol. Immunother. in press. (2000)
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