| Project/Area Number |
12670284
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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 |
Virology
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| Research Institution | Kumamoto University |
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Principal Investigator |
TOMIYAMA Hiroko Viral Immunol., Center for AIDS Research, Kumamoto University, Assistant Professor, エイズ学研究センター, 助手 (50301370)
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| Co-Investigator(Kenkyū-buntansha) |
TAKIGUCHI Masafumi Viral Immunol., Center for AIDS Research, Kumamoto University, Professor, エイズ学研究センター, 教授 (00183450)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | CD8 T cell / inhibition of HIV-1 replication / cytokine / cytotoxic activity / HLA-Class I / down-regulation / nef / escape / 細胞傷害活性 / Nef / HIV-1 / 特異的CD8 T細胞 / テトラマー / perforin / エフェクター細胞 |
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| Research Abstract |
Despite the high frequency of HIV-1 specific CD8^+ T cells were detected, no HIV-1 infected individuals has been ever known to clear away the virus from their body. The mechanism of HIV-1 escape from the recognition of CD8^+ T cells is still unclear. Previous report has demonstrated that primary CD4^+ T cells infected with nef^+ HIV-1 down regulate surface HLA-Class I antigens and are resistant to lysis by HIV-1 specific CTL clones. However it is not unclear whether CTL can recognize HIV-1 infected cells or not. In this study we indicated that HIV-1 specific CTL clones were not able to kill the purified CD4^+ T cells infected with nef ^+ HIV-1(NL-432), while they efficiently lysed CD4^+ T cells infected with nef mutant HIV-1 (NL-M20A) which express functional Nef protein but does not induce the down-regulation of HLA-Class I molecules on infected cells. Cytokine production of these CTL clones by stimulation with NL-432 infected CD4^+ T cells were lower than that by stimulation with NL-M20A infected T cells. These results indicate that the effect of Nef-mediated HLA-Class I down-regulation on infected cells is more affective for killing activity of CTL than that for cytokine production of CTL. Although the replication of NL-M20A was completely suppressed in direct coculture of CTL clone with infected cells, the suppression of NL-432 replication by CTL clone was 50%. These results suggested that HIV-1 specific CD8^+ T cells may partially suppress the replication of nef^+ HIV-1 by production of soluble antiviral factors such as chemokine and cytokine. These findings may explain why HIV-1 specific CD8^+ T cells can control HIV-1 replication in vivo but not completely suppressed HIV-1 replication.
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