1998 Fiscal Year Final Research Report Summary
The development of anti-viral and immuno combined therapy to keep proper function of follicular dendritic cells in mice infected with murine retroviruses.
| Project/Area Number |
09670232
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Kagoshima University |
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Principal Investigator |
MAKINO Masahiko Faculty of Medicine Kagoshima University, Associate Professor, 医学部, 助教授 (60238889)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Murine AIDS / Anti-viral agents / Follicular dendritic cells / CD8^+ killer T cells / Dendritic cells |
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| Research Abstract |
LP-BM5 murine leukemia virus (MuLV) infection causes severe immunodeficiency termed murine AIDS (MAIDS). The acyclic nucleoside phosphonates, (R)-9-(2-p hosphonylmethoxypropyl) adenine (PMPA) and 9-(2-phosphonylmethoxyethyl) adenine (PMEA) were examined, in comparison with zidovudine (AZT), for their inhibitory effect on the development of MAIDS.Although no significant difference in inhibition of LP-BM5 MuLV replication was identified between PMPA and PMEA in cell cultures, PMPA was obviously less cytotoxic to the host lymphocytes. None of the mice treated in vivo with 5 or 25 mg/kg of PMPA or 25 mg/kg of PMEA developed MAIDS at 5 weeks after viral infection. However, at 9 weeks, none of the 25 mg/kg PMPA-treated mice progressed to MAIDS, except for one that developed mild MAIDS, whereas PMEA, even at 100 mg/kg, could not prevent disease progression. MAIDS-associated activation of lymphocytes and viral replication were drastically inhibited by PMPA treatment. Furthermore, the structure of follicular dendritic cells (FDC) and germinal center was normally conserved. These results indicate that PMPA is a highly effective antiretroviral agent in vivo. However, the 25 mg/kg of PMPA treatment starting from 24 hr after viral infection could not inhibit the viral replication and development of MAIDS.Furthermore, in vivo treatment by viral Ag-pulsed dendritic cells (DCs) showed no remarkable therapeutic effect against MAIDS.However, CD8+ killer cells activated by the Ag-pulsed DCs in vitro exhibited temporal anti-MAIDS effect only when they were inoculated directly into lymph node. These results suggest that useful mediators that can selectively activate CD8+ T cells for a long time are absolutely required to treat LP-BM5 MuLV-infected mice.
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[Publications] Suzuki, K., Narita, T., Yui, R., Ohtsuka, K., Inada, S., Kimura, T., Okada, Y., Makino, M., Muzuochi, T., Asakura, H., and Fujiwara, M: "Induction of intestinal lesions in nu/nu mice induced by transfer of lymphocytes from syngenic mice infected with murine retrovirus." GUT. 41 (2). 221-228 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Suruga, Y., Makino, M., Okada, Y., Tanaka, H., De Clercq, E., and Baba, M: "Marked suppression of murine AIDS development by (R)-9-(2-phosphonylmethoxypropyl) adenine." J.AIDS and Hum.Retrovirol.18 (4). 316-322 (1998)
Description
「研究成果報告書概要(欧文)」より
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