| Project/Area Number |
04044129
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | Tokushima University |
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Principal Investigator |
HIMENO Kunisuke School of Medicine, Tokushima University, 医学部, 教授 (50112339)
姫野 国祐 (1993) 徳島大学, 医学部, 教授
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| Co-Investigator(Kenkyū-buntansha) |
MAEDA Ken-ichi School of Medicine, Tokushima University, 医学部, 助手 (30238860)
NAGASAWA Hideyuki School of Medicine, Tokushima University, 医学部, 助教授 (60172524)
AIKAWA Masamichi Case Western Reserve University, Institut, Professor
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 1993: ¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 1992: ¥7,000,000 (Direct Cost: ¥7,000,000)
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| Keywords | heat shock protein / protozoa / protective immunity / low and high virulence / escape / gamma delta T cells / HSP65 / host macrophage / 原虫感染 / γδ型T細胞 / トキソプラズマ / マラリア |
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| Research Abstract |
Toxoplasma gondii is an obligate intracellular protozoan parasite and a serious pathogen of opportunistic infection in compromised hosts like AIDS. Cellular immunity mediated by T cells plays an essential role in protection against this protozoan infection. Mice readily acquire protective immunity against a low-virulence Beverley strain by immunization with Toxoplasma homogenate while live vaccination with sublethal doses of Beverley strain is required for the protection against infection with a high-virulence RH strain.
A 650-kDa heat shock protein (HSP65) was expressed on peritoneal macrophages of BALB/c mice that had been infected with a low-virulence Beverley strain of Toxoplasma gondii or immunized with homogenate of Toxoplasma, as determined by western blot assay using a monoclonal antibody specific for mycobacterial HSP65 and by an immunohistochemical electron microscopy using gold particles. On the other hand, this HSP65 was not expressed when infection had occurred with a high-
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virulence RH strain of T.gondii. HSP65 was, however, expressed even in the infection with RH strain when host mice had acquired resistance against this high-virulence Toxoplasma according to live vaccination with a sublethal dose of Beverley strain. By contrast, when mice were infected with mutant Beverley strain which had acquired high virulence after serial passages into murine peritoneal cavities, these mice lost potentials to express HSP65 on their macrophages. Different from mice, rats are genetically resistant against the infection even with RH strain, and HSP65 was also expressed on their macrophages after infection but not on those of athymic nude rats that are susceptible to such an infection. These results suggest the important role played by HSP65 in developing effective protective immunity against infection with this protozoa in vivo.
Athymic nude mice and SCID mice were susceptible to this infection and they did not show an ability to express HSP65 after infection or immunization. Further, BALB/C mice depleted of T cells, especially gd T cells, became susceptible to the infection even with the low-virulence Beverley strain and HSP65 was scarcely expressed on their macrophages. Thus, T cells, especially gd T cells, play an important role in the induction of HSP65 on host macrophages and in acquiring resistance against Toxoplasma infection. Less
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