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DEFECT OF POST-TRIGGERING NATURAL KILLER CELL MEDIATED CYTOLYTIC ACTIVITY BY SYNTHETIC HIV ANALOGUE PEPTIDES


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Title: DEFECT OF POST-TRIGGERING NATURAL KILLER CELL MEDIATED CYTOLYTIC ACTIVITY BY SYNTHETIC HIV ANALOGUE PEPTIDES
Other Titles: HIVgp41の構成ペプチドおよびその類似合成ペプチドによるヒト末梢血NK活性の抑制機構
Authors: Kiyohara, Tatsuo / Murata, Ken-ichiro / Moriya, Taiichiro / Watanabe, Masami / Ikeda, Shuichi / Ichimaru, Michito / Itakura, Hideyo
Authors (alternative): 清原, 竜夫 / 村田, 建一郎 / 守家, 泰一郎 / 渡辺, 正実 / 池田, 柊一 / 市丸, 道人 / 板倉, 英世
Issue Date: 15-Mar-1991
Publisher: 日本熱帯医学会 / Japanese Society of Tropical Medicine
Citation: 日本熱帯医学会雑誌, vol.19(1), pp.33-38; 1991
Abstract: AIDS患者末梢血NK活性が抑制されている事が知られているが,このNK活性の抑制機構を解析した。無症候性キャリアのNK活性は抑制を受けておらず,その時のキャリアの末梢血のCD4+細胞は0%であった。つぎに, HIVの外殻糖蛋白質gp41の一部で,レトロウイルスに保存されている17個のアミノ酸から成るペプチドと,その類似構造をしたペプチドを3種合成した。これらの合成ペプチドは,正常コントロールのNK活性も,無症候性キャリアのNK活性も共に抑制したが,キャリアに対する抑制が著しかった。正常コントロールNK活性に対する合成ペプチドの作用段階は, NK細胞と標的癌細胞の結合にも,標的細胞によるNK細胞のTriggeringにも合成ペプチドが影響を与えないことから, Triggering以後の段階であると考えられた。一般には, AIDSの発症には,HIVがCD4+細胞に感染し,その機能が損われる事が重要だと考えられており,多くの研究が為されているが,以上の結果より,無症候性キャリアが発症するに至るプロセスには,それ以外のNK等の免疫機能の抑制が何らかの役割を果たしていると考えられた。 / Three kinds of peptides termed ABJ917, ABJ918 and ABJ919 were synthesized and tested their capability of inhibition of Natural Killer (NK) cell mediated cytotoxicity. ABJ917, which is conserved among various retroviral transmembrane envelope proteins inhibited NK activities of the peripheral blood Iymphocytes (PBLs) of both asymptomatic carriers and normal controls. ABJ918 or ABJ919 which correspond to this conserved region also inhibited NK activities. To know the mechanism of inhibition of NK cells by these synthetic peptides, conjugate formation assay and triggering assays were then performed. ABJ917 which inhibited overall NK cytotoxicity did inhibit neither NK and target tumor cell binding nor NK cell triggering by target K562 tumor cells. These results show that the inhibition of NK cytotoxic activity by synthetic HIV peptide is caused in the stage of post-triggering. Peripheral blood CD4+ cell rate of the asymptomatic carriers of HIV was almost 0% when we obtained enough NK activities and these carriers were still quite healthy. Taken together, the immunosuppression of AIDS patients is thought to be caused at least partly from some defects of post-triggering lytic activity of NK cells by HIV transmembrane peptides.
URI: http://hdl.handle.net/10069/22394
ISSN: 03042146
Rights: Japanese Society of Tropical Medicine
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/22394

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