Analysis of the suppression of cell-mediated immunity by street rabies virus infection
Project/Area Number |
02454183
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Research Category |
Grant-in-Aid for General Scientific Research (B)
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Allocation Type | Single-year Grants |
Research Field |
Virology
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Research Institution | Oita Medical University |
Principal Investigator |
MIFUNE Kumato Oita Medical University, Professor School of Medicine, 医学部, 教授 (70039915)
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Co-Investigator(Kenkyū-buntansha) |
SHICHIJO Akehisa Oita Medical University, Professor School of Medicine, 医学部, 助教授 (90039917)
MANNEN Kazuaki Oita Medical University, Associate School of Medicine, 医学部, 助教授 (20145361)
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Project Period (FY) |
1990 – 1992
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Project Status |
Completed (Fiscal Year 1992)
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Budget Amount *help |
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1992: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1991: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1990: ¥4,600,000 (Direct Cost: ¥4,600,000)
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Keywords | Rabies virus / Cell-mediated immunity / Immunosuppression / Inhibition of IL-2 production / IL-2産生抑制 / 狂犬病ウイルス |
Research Abstract |
An attempt to define a severe suppression of cell-mediated immunity by strret rabies virus infection was undertaken by using the mice lethally and peripherally infected with a street virus. The cell-mediated cytotoxic (CMC) activity of the spleen cells from those mice once slightly increased until day 4 after infection but declined rapidly thereafter until their death. In parallel with a decrease of CMC response, proliferative response to ConA, IL-2 activity in the culture supernatant of ConA-induced proliferation, responsiveness to the exogenously added IL-2, and to ConA to express IL-2R, of spleen cells became suppressed, and the marked decrease of the total number of spleen cells was observed. Selective depletion of CD4^+ and CD8^+ cells, abnormalities of IL-1 and PGE_2 production did not appear to be associated with the suppression of proliferative response to ConA. However, an apparent association of CD8^+ cells in the suppression of differentiation of pre-CTL into CTL was demonstrated in the co-culture experiments with spleen cells of mice infected with an attenuated rabied virus which can induce higher levels of CMC response. There was no evidence of the productive replication of rabies virus in thymus and spleen. Mortality of infected mice apparently decreased by four daily administration of IL-2 beginning just after infection and the CMC response of surviving mice was not suppressed. The substance which inhibits ConA-induced proliferation of spleen cells and IL-2 production was produced in the infected mice. It was demonstrated that this substance is produced from CD8^+ cells and is a protein having a molecular weight of more than 10kD. These observation might allow us to speculate that alteration of T cells into a state of defective IL-2 production by some factors, including the IL-2 inhibitor-like substance,is a primary cause of the following cascade of immunosuppressive events.
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Report
(4 results)
Research Products
(5 results)
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[Publications] Hirai,K.,Kawano,H.,Mifune,K.,Fujii,H.,Nishizono,A.,Shichijo,A. and Mannen,K.: "Suppression of cell-mediated immunity by street rabies virus infection" Microbiology and Immunology. 36(12). 1277-1290 (1992)
Description
「研究成果報告書概要(欧文)」より
Related Report
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