2001 Fiscal Year Final Research Report Summary
Recognition of HIV-1 infected CD4 T cells by HIV-1 specific CD8 T cells.
| 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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| Keywords | CD8 T cell / inhibition of HIV-1 replication / cytokine / cytotoxic activity / HLA-Class I / down-regulation / nef / escape |
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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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Research Products
(20 results)
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[Publications] Fukada, K., <Tomiyama. H.>____________-, Wasi, C., Matsuda, T., Kusagawa, S., Sato, H., Oka, S., Takebe, Y., Takiguchi, M: "Ciotoxic T cell recognition of HIV-1 cross -clade and clade-specific epitopes in HIV- 1-infected Thais and Japanese"AIDS. (in press).
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[Publications] Sobao, T., <Tomiyama. H.>____________-, Sugi, K., Tokunaga, M, Ueno, T., Saito, S., Fujiyama, S., Morimoto, M., Tanaka, K., Takiguchi, M.: "The role of Hepatitis B virus-specific memoty CD8 T cells in the control of viral replication"J. Hepatology. 36. 105-115 (2002)
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[Publications] Hossain, M.S., <Tomiyama. H.>____________-, Inagawa, T., Sriwanthana, B., Oka, S., Takiguchi, M: "HLA-A*3303-restricted cytotoxic T lymphocyte recognition for novel epitopes derived from the highly variable region of the HlV-1 Env protein"AIDS. 15. 2199-2208 (2001)
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[Publications] Sobao, Y., Sugi K., <Tomiyama. H.>____________-, Saito, S., Fujiyama, S., Morimoto, M., Hasuike, S., Tsubouchi, H, Tanaka, K., Takiguchi, M: "Identification of hepatitis B virus- specific CTL epitopes preseted by HLA-A*2402, the most common HLA classI allele in East Asia"J. Hepatology. 34. 922-929 (2001)
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[Publications] Maenaka, K., Maenaka, T., <Tomiyama. H.>____________-, Takiguchi, M., Stuart, D.I., Jones, E.Y.: "Nonstandard peptide binding revealed by crystal structures of HLA-B*5101 complexed with HIV immunodominant epitopes"J. Immunol.. 15, 165. 3260-7 (2000)
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「研究成果報告書概要(欧文)」より
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